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Fulltext Review on Bee Products as Potential Protective and Therapeutic Agents in Male Reproductive Impairment

Suleiman JB, Bakar ABA, Mohamed M

Molecules, 2021 Jun 05;26(11).
PMID: 34198728 DOI: 10.3390/molecules26113421

Bee products are sources of functional food that have been used in complementary medicine to treat a variety of acute and chronic illnesses in many parts of the world. The products vary from location to location as well as country to country. Therefore, the aim of this review was to identify various bee products with potential preventive and therapeutic values used in the treatment of male reproductive impairment. We undertook a vigorous search for bee products with preventive and therapeutic values for the male reproductive system. These products included honey, royal jelly, bee pollen, bee brood, apilarnil, bee bread, bee wax, and bee venom. We also explained the mechanisms involved in testicular steroidogenesis, reactive oxygen species, oxidative stress, inflammation, and apoptosis, which may cumulatively lead to male reproductive impairment. The effects of bee pollen, bee venom, honey, propolis, royal jelly, and bee bread on male reproductive parameters were examined. Conclusively, these bee products showed positive effects on the steroidogenic, spermatogenic, oxidative stress, inflammatory, and apoptotic parameters, thereby making them a promising possible preventive and therapeutic treatment of male sub/infertility.
Fulltext A systematic review on different models of inducing obesity in animals: Advantages and limitations

Suleiman JB, Mohamed M, Bakar ABA

J Adv Vet Anim Res, 2020 Mar;7(1):103-114.
PMID: 32219116 DOI: 10.5455/javar.2020.g399

Several animals have been in the limelight of basic research associated with metabolic diseases like obesity. Obesity can be considered as a significant public health concern in the world. It raises the chances for a variety of disease conditions that includes diabetes, hypertension, liver disease, and cancers, which, in turn, decreases the overall lifespan of adult men and women. The World Health Organization has considered obesity as a global epidemic. Researchers have made several attempts to classify human obesity, but none have been successful. Animal obesity can be classified based on their etiology; however, till now, no animal model of obesity can replicate models of the human condition, they have only provided clues into the causes, aftermaths, and preventive remedy to human adiposity. Over the years, there are varieties of animal models used to induce obesity. Some of them include monogenic, polygenic, surgical, seasonal, and other models of obesity. Apart from the advantages of these models, most of them are accompanied by limitations. The primary purpose of this review is, therefore, to highlight the several models with their advantages and limitations. By knowing the benefits and limitations of animal models of obesity, researchers may be at liberty to select the appropriate one for the study of obesity.
Obesity-induced testicular oxidative stress, inflammation and apoptosis: Protective and therapeutic effects of orlistat

Suleiman JB, Nna VU, Zakaria Z, Othman ZA, Bakar ABA, Mohamed M

Reprod Toxicol, 2020 08;95:113-122.
PMID: 32450208 DOI: 10.1016/j.reprotox.2020.05.009

Obesity has been reported to induce oxidative stress, inflammation and apoptosis in the testis. The objective of this study was to determine the effects of the anti-obesity drug orlistat, on testicular oxidative stress, inflammation and apoptosis in high-fat diet (HFD)-fed rats. Twenty-four adult male Sprague Dawley rats weighing 250-300 g were randomized into four groups (n = 6/group), namely; normal control (NC), high-fat diet (HFD), HFD plus orlistat (10 mg/kg body weight/day administered concurrently for 12 weeks) (HFD + Opr) and HFD plus orlistat (10 mg/kg body weight/day administered 6 weeks after induction of obesity) (HFD + Ot) groups. Antioxidant enzymes activities were significantly decreased, while mRNA levels of pro-apoptotic markers (p53, Bax/BCl-2, caspase-9, caspase-8 and caspase-3) were significantly increased in the testis of HFD group relative to NC group. Furthermore, the mRNA levels of pro-inflammatory markers (nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis factor alpha and interleukin (IL)-1β increased significantly, while anti-inflammatory marker (IL-10) decreased significantly in the testis of the HFD group relative to NC group. However, in both models of orlistat intervention (protective and treatment models) up-regulated antioxidant enzymes, down-regulated inflammation and apoptosis were observed in the testis of HFD-fed rats. Orlistat ameliorated testicular dysfunction by attenuating oxidative stress, inflammation and apoptosis in HFD-fed rats, suggesting its potential protective and therapeutic effects in the testis compromised by obesity.
Fulltext Bee Bread Ameliorates Vascular Inflammation and Impaired Vasorelaxation in Obesity-Induced Vascular Damage Rat Model: The Role of eNOS/NO/cGMP-Signaling Pathway

Othman ZA, Zakaria Z, Suleiman JB, Nna VU, Che Romli A, Wan Ghazali WS, et al.

Int J Mol Sci, 2021 Apr 19;22(8).
PMID: 33921777 DOI: 10.3390/ijms22084225

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role.
Orlistat attenuates obesity-induced decline in steroidogenesis and spermatogenesis by up-regulating steroidogenic genes

Suleiman JB, Nna VU, Othman ZA, Zakaria Z, Bakar ABA, Mohamed M

Andrology, 2020 09;8(5):1471-1485.
PMID: 32438512 DOI: 10.1111/andr.12824

BACKGROUND: Steroidogenesis decline is reported to be one of the mechanisms associated with obesity-induced male factor subfertility/infertility.
OBJECTIVES: We explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity-induced steroidogenesis and spermatogenesis decline.
MATERIALS AND METHODS: Twenty-four adult male Sprague Dawley rats weighing 250-300 g were randomized into four groups (n = 6/group), namely; normal control, high-fat diet, high-fat diet plus orlistat preventive group and high-fat diet plus orlistat treatment group. Orlistat (10 mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high-fat diet for 12 weeks (high-fat diet plus orlistat preventive group) or administered from week 7-12 post- high-fat diet feeding (high-fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses.
RESULTS: Obesity increased serum leptin and decreased adiponectin levels, decreased serum and intra-testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were significantly decreased in the testes of the high-fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high-fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high-fat diet-induced obese male rats, with the preventive group (high-fat diet plus orlistat preventive group) having better results relative to the treatment group (high-fat diet plus orlistat treatment group).
DISCUSSION AND CONCLUSION: Orlistat attenuated impaired spermatogenesis and steroidogenesis decline by up-regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.
Orlistat reverses intratesticular lactate transport decline and infertility in male obese rats

Suleiman JB, Nna VU, Zakaria Z, Othman ZA, Bakar ABA, Usman UZ, et al.

Reproduction, 2020 12;160(6):863-872.
PMID: 33112813 DOI: 10.1530/REP-20-0381

Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague-Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.
Effect of bee bread on some biochemical parameters and skeletal muscle histology of high-fat diet-induced obese Sprague-Dawley rats

Eleazu C, Suleiman JB, A Othman Z, Zakaria Z, Nna VU, Mohamed M

J Food Biochem, 2021 02;45(2):e13626.
PMID: 33492697 DOI: 10.1111/jfbc.13626

The effect of bee bread (BB) on the biochemical parameters-body weights, calorie intake, Lee obesity indices, serum amylase, aspartate and alanine amino transferases, skeletal muscle activities of creatine kinase, superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, glutathione-S-transferase, total antioxidant activity, endogenous secretory receptor for advanced glycation end products (esRAGE), and muscle histology of high-fat diet (HFD) obese rats-was studied. Thirty-six male Sprague-Dawley rats were divided into six groups: Control: received rat feed and water (1 ml/kg); HFD: received HFD and water (1 ml/kg): BB or orlistat preventive: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg; weeks 1 to 12); BB or orlistat treated: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg; weeks 6 to 12), following obesity induction. At week 12, HFD group had altered (p
Fulltext Chemical Profile, Antioxidant Properties and Antimicrobial Activities of Malaysian Heterotrigona itama Bee Bread

Suleiman JB, Mohamed M, Abu Bakar AB, Nna VU, Zakaria Z, Othman ZA, et al.

Molecules, 2021 Aug 15;26(16).
PMID: 34443531 DOI: 10.3390/molecules26164943

The aim of the study was to determine the chemical profile, antioxidant properties and antimicrobial activities of Heterotrigona itama bee bread from Malaysia. The pH, presence of phytochemicals, antioxidant properties, total phenolic content (TPC) and total flavonoid content (TFC), as well as antimicrobial activities, were assessed. Results revealed a decrease in the pH of bee bread water extract (BBW) relative to bee bread ethanolic extract (BBE) and bee bread hot water extract (BBH). Further, alkaloids, flavonoids, phenols, tannins, saponins, terpenoids, resins, glycosides and xanthoproteins were detected in BBW, BBH and BBE. Also, significant decreases in TPC, TFC, DPPH activity and FRAP were detected in BBW relative to BBH and BBE. We detected phenolic acids such as gallic acid, caffeic acid, trans-ferulic acid, trans 3-hydroxycinnamic acid and 2-hydroxycinnamic acid, and flavonoids such as quercetin, kaempferol, apigenin and mangiferin in BBE using high-performance liquid chromatography analysis. The strongest antimicrobial activity was observed in Klebsilla pneumonia (MIC50 1.914 µg/mL), followed by E. coli (MIC50 1.923 µg/mL), Shigella (MIC50 1.813 µg/mL) and Salmonella typhi (MIC50 1.617 µg/mL). Bee bread samples possess antioxidant and antimicrobial properties. Bee bread contains phenolic acids and flavonoids, and could be beneficial in the management and treatment of metabolic diseases.
Bee bread attenuates high fat diet induced renal pathology in obese rats via modulation of oxidative stress, downregulation of NF-kB mediated inflammation and Bax signalling

Eleazu C, Suleiman JB, Othman ZA, Zakaria Z, Nna VU, Hussain NHN, et al.

Arch Physiol Biochem, 2020 Apr 22.
PMID: 32319823 DOI: 10.1080/13813455.2020.1752258

Context: Global prevalence of obesity is increasing. Objective: To study the effect of bee bread (BB) on serum renal function parameters, oxidative stress, inflammatory and B-cell associated protein X (Bax) in the kidneys of high fat diet (HFD) obese rats. Methods: Thirty-six male Sprague Dawley rats were used. Control: received rat diet and water (1 mL/kg); HFD group: received HFD and water (1 mL/kg): bee bread (BB) preventive or orlistat preventive: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg); BB or orlistat treatment: received BB (0.5 g/kg) or orlistat (10 mg/kg). Results: HFD group had increased body weight, Body Mass Index, Lee Obesity Indices, kidney weights, malondialdehyde, inflammatory markers, Bax; decreased glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, total antioxidant activity, no differences (p > .05) in food intakes, serum creatinine, sodium, potassium, chloride, catalase compared to control. Conclusion: BB modulated most of these parameters, as corroborated by histology.
Fulltext Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation

Zakaria Z, Othman ZA, Suleiman JB, Che Jalil NA, Ghazali WSW, Nna VU, et al.

Antioxidants (Basel), 2021 Dec 20;10(12).
PMID: 34943134 DOI: 10.3390/antiox10122031

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis.
Bee bread attenuates the progression of atherosclerosis by activating Nrf2/Keap1 and modulating TNF-α/NF-κβ-associated mast cell migration and a mitochondrial-dependent apoptotic pathway in the obese rat model

Othman ZA, Zakaria Z, Suleiman JB, Che Jalil NA, Wan Ghazali WS, Mohamed M

Food Funct, 2022 Aug 01;13(15):8119-8130.
PMID: 35796099 DOI: 10.1039/d2fo00949h

This study explores the anti-atherosclerotic effects of bee bread in the context of oxidative stress, inflammation, and apoptosis phenomena in an obesity animal model, and its vitamin composition. Forty male Sprague-Dawley rats were administered with a normal diet (Normal group) and a high-fat diet (HFD) to induce obesity. After 6 weeks, obese rats that received the HFD were treated either with distilled water (Ob group), bee bread at 0.5 g per kg per day (Ob + Bb group), or orlistat at 10 mg per kg per day (Ob + Or group) concomitant with the HFD for another 6 weeks. Bee bread significantly improved atherosclerotic changes by enhancing the immunoexpressions of Nrf2/Keap1, impeding the immunoexpressions of NF-κβ downstream proteins, and intensifying Bcl-2 upregulation, attributed to the improvement in mast cell adherence and collagen deposition in the aortic wall of the Ob + Bb group. We have demonstrated that the treatment with bee bread attenuates the progression of atherosclerosis through its inhibition of vascular oxidative stress, and retardation of inflammatory reaction and apoptosis in obese rats, indicating its potential therapeutic targets for obesity-related vascular diseases. This could be partly attributed to the components of vitamins such as vitamins A, C and E that are present in bee bread, which need further study for the exact molecular mechanism of action.
Fulltext Malaysian propolis and metformin mitigate subfertility in streptozotocin-induced diabetic male rats by targeting steroidogenesis, testicular lactate transport, spermatogenesis and mating behaviour

Nna VU, Bakar ABA, Ahmad A, Umar UZ, Suleiman JB, Zakaria Z, et al.

Andrology, 2020 05;8(3):731-746.
PMID: 31816190 DOI: 10.1111/andr.12739

BACKGROUND: Diabetes mellitus is one of the risk factors for male subfertility/infertility. Malaysian propolis is reported to decrease hyperglycaemia in diabetic state.
OBJECTIVES: The present study investigated the protective effect of Malaysian propolis on diabetes-induced subfertility/infertility. Additionally, its combined beneficial effects with metformin were investigated.
MATERIALS AND METHODS: Forty adult male Sprague Dawley rats were randomly assigned into five groups, namely normal control, diabetic control, diabetic + Malaysian propolis (300 mg/k.g. b.w.), diabetic + metformin (300 mg/kg b.w.) and diabetic + Malaysian propolis + metformin. Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.) and treatment lasted for 4 weeks. During the 4th week, mating behavioural experiments were performed using sexually receptive female rats. Thereafter, fertility parameters were assessed in the female rats.
RESULTS: Malaysian propolis increased serum and intratesticular free testosterone levels, up-regulated the mRNA levels of AR and luteinizing hormone receptor, up-regulated the mRNA and protein levels of StAR, CYP11A1, CYP17A1, 3β-HSD and 17β-HSD in the testes of diabetic rats. Furthermore, Malaysian propolis up-regulated testicular MCT2, MCT4 and lactate dehydrogenase type C mRNA levels, in addition to improving sperm parameters (count, motility, viability and normal morphology) and decreasing sperm nDNA fragmentation in diabetic rats. Malaysian propolis improved mating behaviour by increasing penile guanosine monophosphate levels. Malaysian propolis also improved fertility outcome as seen with decreases in pre- and post-implantation losses, increases in gravid uterine weight, litter size per dam and foetal weight. Malaysian propolis's effects were comparable to metformin. However, their combination yielded better results relative to the monotherapeutic interventions.
CONCLUSION: Malaysian propolis improves fertility potential in diabetic state by targeting steroidogenesis, testicular lactate metabolism, spermatogenesis and mating behaviour, with better effects when co-administered with metformin. Therefore, Malaysian propolis shows a promising complementary effect with metformin in mitigating Diabetes mellitus-induced subfertility/infertility.
Fulltext Bee bread mitigates downregulation of steroidogenic genes, decreased spermatogenesis, and epididymal oxidative stress in male rats fed with high-fat diet

Suleiman JB, Abu Bakar AB, Noor MM, Nna VU, Othman ZA, Zakaria Z, et al.

Am J Physiol Endocrinol Metab, 2021 Sep 01;321(3):E351-E366.
PMID: 34229480 DOI: 10.1152/ajpendo.00093.2021

The pituitary-gonadal axis plays an important role in steroidogenesis and spermatogenesis, and by extension, fertility. The aim of this study was to investigate the protective role of bee bread, a natural bee product, against obesity-induced decreases in steroidogenesis and spermatogenesis. Thirty-two adult male Sprague-Dawley rats weighing between 200 and 300 g were divided into four groups (n = 8/group), namely: normal control (NC), high-fat diet (HFD), HFD plus bee bread administered concurrently for 12 wk (HFD + B), HFD plus orlistat administered concurrently for 12 wk (HFD + O) groups. Bee bread (0.5 g/kg) or orlistat (10 mg/kg/day) was suspended in distilled water and given by oral gavage daily for 12 wk. Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and adiponectin, as well as sperm count, motility, viability, normal morphology, and epididymal antioxidants decreased, whereas levels of leptin, malondialdehyde, and sperm nDNA fragmentation increased significantly in the HFD group relative to the NC group. There were significant decreases in the testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme, 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD in the testes of the HFD group. Furthermore, mount, intromission and ejaculatory latencies increased, and penile cGMP level decreased significantly in the HFD group. Supplementation with bee bread significantly reduced leptin level and increased adiponectin level, enhanced sperm parameters and reduced sperm nDNA fragmentation, upregulated the levels of steroidogenic genes and proteins in HFD-induced obese male rats. Bee bread improved steroidogenesis and spermatogenesis by upregulating steroidogenic genes. Therefore, bee bread may be considered as a potential supplementation to protect against infertility in overweight men or men with obesity.NEW & NOTEWORTHY The high-fat diet utilized in the present study induced obesity in the male rats. Bee bread supplementation mitigated impaired steroidogenesis, spermatogenesis, mating behavior, and fertility potential by counteracting the downregulation of steroidogenic genes, thus increasing testosterone levels and suppressing epididymal oxidative stress. These benefits may be due to the abundance of phenolic and flavonoid compounds in bee bread.
Tert-butylhydroquinone preserve testicular steroidogenesis and spermatogenesis in cisplatin-intoxicated rats by targeting oxidative stress, inflammation and apoptosis

Nna VU, Ujah GA, Suleiman JB, Mohamed M, Nwokocha C, Akpan TJ, et al.

Toxicology, 2020 08;441:152528.
PMID: 32565124 DOI: 10.1016/j.tox.2020.152528

Cisplatin (Cis) is an effective chemotherapeutic intervention against many cancer types. However, the oxidative stress-related toxicities associated with cancer cell resistance-induced dose scaling has limited its long-term use. In the present study, we explored the benefits of the antioxidant, tert-butylhydroquinone (tBHQ; 50 mg/kg b.w./day, for 14 days) against Cis single dose injection (7 mg/kg b.w., i.p on Day 8), on testicular toxicity of male Wistar rats. Cis triggered testicular and epididymal oxidative stress, testicular inflammation (upregulated NF-κB, TNF-α and IL-1β mRNA levels, and downregulated IL-10 mRNA level), increased testicular apoptosis (increased Bax/Bcl2 and caspase-3 mRNA levels) and decreased testicular germ cells proliferation. Further, Cis decreased testicular steroidogenesis (decreased expression of StAR, CYP11A1, 3β-HSD and 17β-HSD mRNA and proteins) and decreased follicle stimulating hormone, luteinizing hormone and testosterone levels. Cis also decreased sperm count, motility, viability, normal morphology and Johnsen score. However, intervention with tBHQ significantly decreased oxidative stress by upregulating Nrf2 gene, suppressed inflammation, apoptosis and increased testicular germ cells proliferation. tBHQ also increased steroidogenesis and improved sperm parameters. Taken together, tBHQ improves steroidogenesis and spermatogenesis in Cis-intoxicated rats by improving antioxidant status, dampening inflammation and apoptosis, thus improving the proliferative capacity of spermatogenic cells.
Fulltext Tert-butylhydroquinone attenuates doxorubicin-induced dysregulation of testicular cytoprotective and steroidogenic genes, and improves spermatogenesis in rats

Ujah GA, Nna VU, Suleiman JB, Eleazu C, Nwokocha C, Rebene JA, et al.

Sci Rep, 2021 Mar 09;11(1):5522.
PMID: 33750916 DOI: 10.1038/s41598-021-85026-7

Doxorubicin (DOX) is a broad-spectrum chemotherapeutic drug used in the treatment of cancers. It acts by generating reactive oxygen species in target cells. The actions are, however, not limited to cancerous cells as it attacks healthy cells, killing them. This study investigated the benefits of the antioxidant, tert-butylhydroquinone (tBHQ), on testicular toxicity following DOX therapy. Twenty-four adult male albino rats were assigned randomly into four groups (n = 6), namely: normal control (NC), tBHQ, DOX and tBHQ + DOX groups. tBHQ (50 mg/kg body weight in 1% DMSO) was administered orally for 14 consecutive days, while a single DOX dose (7 mg/kg body weight) was administered intraperitoneally on Day 8. DOX decreased sperm count, motility and viability, and decreased the levels of steroidogenesis-related proteins, and reproductive hormones. Furthermore, DOX decreased the expression of antioxidant cytoprotective genes, and decreased the protein level of proliferating cell nuclear antigen in the testis. Conversely, DOX increased the expression of pro-inflammatory and pro-apoptotic genes in the testis. These negative effects were ameliorated following the intervention with tBHQ. Our results suggest that tBHQ protects the testis and preserves both steroidogenesis and spermatogenesis in DOX-treated rats through the suppression of oxidative stress, inflammation and apoptosis.

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