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Fulltext Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine

Koriem KM, Soliman RE

J Toxicol, 2014;2014:583494.
PMID: 25136360 DOI: 10.1155/2014/583494

Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven-day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective.
Fulltext Toxicity of Metals to a Freshwater Ostracod: Stenocypris major

Shuhaimi-Othman M, Yakub N, Ramle NA, Abas A

J Toxicol, 2011;2011:136104.
PMID: 21559091 DOI: 10.1155/2011/136104

Adults of freshwater ostracod Stenocypris major (Crustacea, Candonidae) were exposed for a four-day period in laboratory conditions to a range of copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al), and manganese (Mn) concentrations. Mortality was assessed, and median lethal times (LT(50)) and concentrations (LC(50)) were calculated. LT(50) and LC(50) increased with the decrease in mean exposure concentrations and times, respectively, for all metals. LC(50)s for 96 hours for Cu, Cd, Zn, Pb, Ni, Fe, Al, and Mn were 25.2, 13.1, 1189.8, 526.2, 19743.7, 278.9, 3101.9, and 510.2 μg/L, respectively. Metals bioconcentration in S. major increases with exposure to increasing concentrations, and Cd was the most toxic to S. major, followed by Cu, Fe, Mn, Pb, Zn, Al, and Ni (Cd>Cu>Fe>Mn>Pb>Zn>Al>Ni). Comparison of LC(50) values for metals for this species with those for other freshwater crustacean reveals that S. major is equally or more sensitive to metals than most other tested crustacean.
Fulltext Effects of cytochrome p450 inhibitors on itraconazole and fluconazole induced cytotoxicity in hepatocytes

Somchit N, Ngee CS, Yaakob A, Ahmad Z, Zakaria ZA

J Toxicol, 2009;2009:912320.
PMID: 20130764 DOI: 10.1155/2009/912320

Itraconazole and fluconazole have been reported to induce hepatotoxicity in patients. The present study was designed to investigate the role of cytochrome P450 inhibitors, SKF 525A, and curcumin pretreatment on the cytotoxicity of antifungal drugs fluconazole and itraconazole. For 3 consecutive days, female rats were administered daily SKF 525A or curcumin (5 and 25 mg/kg). Control rats received an equivalent amount of dosed vehicle. The animals were anaesthetized 24 hours after receiving the last dose for liver perfusion. Hepatocytes were then exposed to various concentrations of antifungal drugs. In vitro incubation of hepatocytes with itraconazole revealed significantly lower viability when compared to fluconazole as assessed by lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase activities. The cytotoxicity of itraconazole was enhanced when incubated with hepatocytes pretreated with SKF 525A. SKF 525A had no effects on the cytotoxicity of fluconazole. Curcumin failed to either increase or decrease the cytotoxicity of both antifungal drugs. ATP levels also showed significant decrease in both itraconazole and fluconazole incubated hepatocytes. However, SKF 525A pretreated hepatocytes had significantly lower ATP levels after itraconazole incubations. Collectively, these results confirm the involvement of cytochrome P450 in the cytoprotection in itraconazole induced hepatocyte toxicity. Differences of the effects of SKF 525A on the cytotoxicity induced by itraconazole and fluconazole may be due to the differences on the metabolism of each antifungal drug in vivo.
Fulltext Biochemical Constituent of Ginkgo biloba (Seed) 80% Methanol Extract Inhibits Cholinesterase Enzymes in Javanese Medaka (Oryzias javanicus) Model

Hassan I, Wan Ibrahim WN, Yusuf FM, Ahmad SA, Ahmad S

J Toxicol, 2020;2020:8815313.
PMID: 33029137 DOI: 10.1155/2020/8815313

Background: Pathophysiological changes leading to the death of nerve cells present in the brain and spinal cord are referred to as neurodegenerative diseases. Presently, treatment of these diseases is not effective and encounters many challenges due to the cost of drug and side effects. Thus, the search for the alternative agents to replace synthetic drugs is in high demand. Therefore, the aim of this study is to evaluate the anticholinesterase properties of Ginkgo biloba seed.
Methods: The seed was extracted with 80% methanol. Toxicity studies and evaluation of anticholinesterase activities were carried out in adult Javanese medaka (Oryzias javanicus). Phytochemical study to identify the bioactive lead constituents of the crude extract was also carried out using high performance liquid chromatography (HPLC).
Results: The result shows activities with high significant differences at P < 0.001 between the treated and nontreated groups. A bioactive compound (vitaxin) was identified with the aid of HPLC method.
Conclusion: The presence of bioactive compound vitaxin is among the major secondary metabolites that contribute to increasing activities of this plant extract. High anticholinesterase activities and low toxicity effect of this plant show its benefit to be used as natural medicine or supplements.
Antioxidant Potential, Subacute Toxicity, and Beneficiary Effects of Methanolic Extract of Pomelo (Citrus grandis L. Osbeck) in Long Evan Rats

Ali MY, Rumpa NN, Paul S, Hossen MS, Tanvir EM, Hossan T, et al.

J Toxicol, 2019;2019:2529569.
PMID: 31281355 DOI: 10.1155/2019/2529569

The aim of this study was to investigate the antioxidant potentials, subacute toxicity, and beneficiary effects of methanolic extract of pomelo (Citrus grandis L. Osbeck) in rats. Long Evans rats were divided into four groups of eight animals each. The rats were orally treated with three doses of pomelo (250, 500, and 1000 mg/kg) once daily for 21 days. Pomelo extract contained high concentrations of polyphenols, flavonoids, and ascorbic acid while exhibiting high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power values. There was no significant change in the body weight, percentage water content, and relative organ weight at any administered doses. In addition, no significant alterations in the hematological parameters were also observed. However, rats which received 1000 mg/kg dose had a significant reduction in some serum parameters, including alanine transaminase (15.29%), alkaline phosphatase (2.5%), lactate dehydrogenase (15.5%), γ-glutamyltransferase (20%), creatinine (14.47%), urea (18.50%), uric acid (27.14%), total cholesterol (5.78%), triglyceride (21.44%), low-density lipoprotein cholesterol (40.74%), glucose (2.48%), and all atherogenic indices including cardiac risk ratio (24.30%), Castelli's risk index-2 (45.71%), atherogenic coefficient (42%), and atherogenic index of plasma (25%) compared to control. In addition, the highest dose (1000 mg/kg) caused a significant increase in iron (12.07%) and high-density lipoprotein cholesterol (8.87%) levels. Histopathological findings of the vital organs did not indicate any pathological changes indicating that pomelo is nontoxic, safe, and serves as an important source of natural antioxidants. In addition, the fruit extract has the potential to ameliorate hepato- and nephrotoxicities and cardiovascular diseases as well as iron deficiency anemia.
Fulltext Risk Assessment of Kumasi Metropolis Population in Ghana through Consumption of Fish Contaminated with Formaldehyde

Asare-Donkor NK, Adaagoam RA, Voegborlo RB, Adimado AA

J Toxicol, 2018;2018:4785031.
PMID: 30515208 DOI: 10.1155/2018/4785031

This study evaluates the exposure of the Ghanaian population of the Kumasi Metropolis of Ghana to formaldehyde through the consumption of fish using 3-Methyl-2-Benzothiazoline Hydrazone method, with trichloroacetic acid as an extracting agent. A total of sixty (60) fish species comprising both local and imported fish were bought from cold stores and fish ponds were analysed. Formaldehyde was found in all the species analysed with concentration ranging from 0.174 to 3.710 μgg-1. However, the levels were still lower than 5 mg/kg, which is the maximum limit established by the Malaysian Food Act and Regulation for formaldehyde in fish. The estimated daily intake values for formaldehyde in the fish species analysed ranged between 4.233 × 10-4 and 3.661 × 10-3 mg/kg BW/day and this was less than the acceptable daily intake of 0.15 and 0.2 mg/kg BW/day suggested by World Health Organization and the United States Environmental Protection Agency for formaldehyde intake, respectively. The results for the hazard quotient calculated for all the species were less than one suggesting that the amount of formaldehyde in the fish is not likely to pose any potential adverse health effects to consumers. Thus, wet fish from Kumasi may be considered safe for consumption because of low formaldehyde content.
Fulltext Histological, Biochemical, and Hematological Effects of Goniothalamin on Selective Internal Organs of Male Sprague-Dawley Rats

Kaid F, Alabsi AM, Alafifi N, Ali-Saeed R, Ameen Al-Koshab M, Ramanathan A, et al.

J Toxicol, 2019;2019:6493286.
PMID: 31178909 DOI: 10.1155/2019/6493286

Goniothalamin (GTN) is an isolated compound from several plants of the genus Goniothalamus, and its anticancer effect against several cancers was reported. However, there is no scientific data about effects of its higher doses on internal organs. Accordingly, this study aimed to evaluate the acute and subacute effects of higher doses of GTN on the hematology, biochemistry, and histology of selected internal organs of male Sprague-Dawley rats. In acute study, 35 rats were distributed in 5 groups (n=7) which were intraperitoneally (IP) injected with a single dose of either 100, 200, 300, 400, or 500 mg/kg of GTN, while extra 7 rats serve as a normal control. In subacute study, 7 rats were IP-injected with a daily dose of 42 mg/kg of GTN for 14 days, while another 7 rats serve as a normal control group. The normal controls in both studies were IP-injected simultaneously with 2 ml/kg of 10% DMSO in PBS. At the end of both tests, rats were sacrificed to collect blood for hematology and biochemistry and harvest livers, kidneys, lungs, hearts, spleens, and brains for histology. During acute and subacute exposure, no abnormal changes were observed in the hematology, biochemistry, and histology of the internal organs. However, the 300, 400, and 500 mg/kg of GTN during acute exposure were associated with morbidities and mortalities. Ultimately, GTN could be safe up to the dose of 200 mg/kg, and the dose of 42 mg/kg of GTN was tolerated well.
Fulltext Sublethal Effects of Cadmium on the Osmoregulatory and Acid-Base Parameters of Tilapia (Oreochromis niloticus) at Various Times

Soegianto A, Yulianto B, Payus CM, Affandi M, Mukholladun W, Indriyasari KN, et al.

J Toxicol, 2023;2023:2857650.
PMID: 36891516 DOI: 10.1155/2023/2857650

BACKGROUND: Cadmium (Cd) can contaminate aquatic environments as a result of anthropogenic activity. Cd accumulates quickly in the tissues of fish and has the potential to affect their physiology, including osmoregulation and acid-base balance. Therefore, the purpose of this study was to examine the sublethal effects of Cd on the osmoregulation and acid-base balance of tilapia Oreochromis niloticus at different times.
METHODS: Fish were exposed to sublethal concentrations of Cd (1 and 2 mg/L) for 4 and 15 days. At the end of the experiment, fish were collected from each treatment to examine the levels of Cd and carbonic anhydrase (CA) in the gills, plasma osmolality, ions, blood pH, pCO2, pO2, and hematological parameters.
RESULTS: Cd concentrations in gills rose with increasing Cd concentrations in the medium and exposure time. Cd inhibited respiration by generating metabolic acidosis, decreasing gill CA, reducing pO2, plasma osmolality, Cl-, and K+, particularly at 2 mg/L for 4 days and 1 and 2 mg/L for 15 days. Red blood cell (RBC), hemoglobin (Hb), and hematocrit (Ht) levels decreased as Cd levels in water and exposure duration increased.
CONCLUSION: Cd inhibits respiration, lowers RCB, Hb, and Ht levels and decreases ionic and osmotic regulation. All of these impairments can limit a fish's ability to provide appropriate oxygen to its cells, hence diminishing its physical activity and productivity.