Although this paper makes a special appeal to workers in Malaya it will be found interesting and instructive by the many medical men elsewhere who have been perplexed by the confusing nomenclature of rats and related animals. The author describes the following, which are the six common house and field animals of Malaya popularly called "rats ". A. Rodentia: Muridae. (1) Rattus rattus (Sp. R.r. diardi; R. r. argentiventer; R. r. jalorensis. (2) R. norvegicus. (3) R. exulans. (4) Mus musculus. (5) Bandicota bengalensis. B. Insectivora: Soricidae. (6) Suncus caeruleus, the musk shrew which is grossly slandered by being called a rat; it is an insectivore and the author states that there is no evidence of its being concerned in the transmission of any disease. A clear description is given of the habits, external appearance, skull characters, and association, if any, with disease, of each of the above animals. The animals chiefly concerned in the transmission of disease in Malaya are stated as being R. r. diardi (murine typhus), and R. r. argentiventer, (scrub typhus and probably leptospirosis). Plague is not occurring at present in Malaya. Medical men in Malaya are fortunate in being provided in this and other papers with simple practical guides to the local fauna which are important from the public health point of view. [See also this Bulletin, 1949, v. 46, 245, 247.] John W. D. Megaw.
BACKGROUND: Glucuronidation catalyzed by uridine 5'- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
OBJECTIVE: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
MATERIALS AND METHODS: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
RESULTS: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
CONCLUSIONS: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
KEYWORDS: 4-methylumbelliferone; 7-hydroxymitragynine; buprenorphine; glucuronidation; ketamine; mitragynine
Mitragyna speciosa Korth is a medicinal plant indigenous to Thailand and Malaysia and has been known for its narcotic and coca-like effects. Many studies have been performed on the antinociceptive effect of the plant extracts of Thai origin; however, limited studies have been reported till date on M. speciosa extracts of Malaysian origin. Various concentrations of alkaloid (5-20 mg/kg), methanolic (50-200 mg/kg), and aqueous (100-400 mg/kg) extracts of Malaysian M. speciosa leaves were prepared and orally administered to nine groups of rats. Morphine (5 mg/kg, s.c.) and aspirin (300 mg/kg, p.o.) were used as control. Antagonism of the antinociceptive activity was evaluated by pretreatment with naloxone at a dose of 2 mg/kg (i.p.). Results showed that oral administration of the alkaloid (20 mg/kg), methanolic (200 mg/kg), and aqueous (400 mg/kg) extracts significantly prolonged the latency of nociceptive response compared with control groups in both hot plate and tail flick tests (P < 0.05). Antinociceptive action of the alkaloid (20 mg/kg), methanolic (200 mg/kg), and aqueous (400 mg/kg) extracts was significantly blocked by naloxone. In conclusion, these results suggest the presence of antinociceptive effect in various extracts of Malaysian M. speciosa leaves. In addition, the antinociceptive effective doses vary depending on the type of solvents used for extraction.
In a previous paper the authors reported on the methods and zoogeographical background of a survey of animal leptospirosis in Malaya, giving a broad analysis of results. In the present paper the localities studied in towns and villages, in ricefields, in secondary forest and scrub and in primary forest are compared in detail. In towns and villages infection rates in rats were low, except in a seaport town where the invading R. norvegicus was heavily infected. In ricefields infection is maintained in R. argentiventer, alone or in association with R. exulans. In secondary forest and scrub there is overlap with forest species and the main hosts of leptospires appear to be R. exulans and R. jalorensis. In primary forest giant rats and, to a lesser degree, spiny rats are the main hosts.Ground-living rats appear to be better maintenance hosts than those scrambling on vegetation or arboreal rats. With some exceptions the incidence of infection of a rat species in an area was found to be in direct relation to the proportion that species formed of the total rat population. The critical number of rats for maintenance of leptospirosis in an area is estimated to be about two rats of the maintenance species per hectare.
Breinlia booliati Singh & Ho, 1973 first described from Peninsular Malaysia has been shown to infect a large range of murids ranging in distribution from southern Thailand, Peninsular Malaysia, Sarawak to Ciloto, Indonesia. Probably further work will reveal a greater host range as well as its geographical distribution. The vectors involved in its transmission need to be elucidated.
Aflatoxin B1(AFB1) is a toxic compound commonly found in some crops with an adverse health effect on human and animals. Some beneficial microorganisms (or probiotics) such as lactic acid bacteria have shown the ability to reduce the bioavailability of aflatoxins and its intestinal absorption. However, the dose and duration of aflatoxins exposure and probiotic treatment can influence the ability of probiotics to remove aflatoxins. Therefore, this research aimed to investigate the efficacy of oral probiotic Lactobacillus casei Shirota strain (LcS) induction in an acute exposure to AFB1 in rats. Experimentally, Sprague Dawley rats were divided into three groups: AFB1 only (n = 9); AFB1 treated with LcS (n = 9); and control (no AFB1 exposure) (n = 6) groups. The blood AFB1 level of rats treated with LcS was slightly lower than the untreated AFB1 induced rats (11.12 ± 0.71 vs 10.93 ± 0.69 ng g-1). Also, LcS treatment slightly moderated the liver and kidney biomarkers in AFB1 induced rats. However, a trend for a significant difference was only observed in ALT of AFB1 induced rats treated with LcS compared to their counterparts (126.11 ± 36.90 vs 157.36 ± 15.46, p = 0.06). Rats' body weight decreased in all animals force-fed with AFB1 with no significant difference between LcS treatment compared to the counterpart. In conclusion, this experiment indicated that probiotic LsC was able to slightly ameliorate the adverse effect of an acute exposure to AFB1 in rats. However, future studies with longer probiotics treatment or higher probiotics dose is required to confirm these findings.
Hiperkolesterolemia merupakan suatu keadaan yang dikaitkan dengan perubahan aras lipid serum serta peningkatan aras peroksidaan lipid. Kajian ini dilakukan untuk melihat kesan ekstrak akues isi dan kulit buah Hylocereus polyrhizus (HP) terhadap jumlah kolesterol dan trigliserid (TG) serum serta aras malonaldehid (MDA-TBAR) hati tikus teraruh hiperkolesterolemia. Tikus Sprague dawley jantan diaruh menjadi hiperkolesterolemia dengan pemberian diet rat chow bersama 15% minyak sapi selama 8 minggu dan 0.02 g kolesterol secara suap paksa dua kali seminggu. Tikus-tikus diberi perlakuan ekstrak isi dan kulit buah HP, 300 mg/kg secara suap paksa selama 10 hari. Hasil menunjukkan aras kolesterol menurun secara signifikan (p<0.05) pada kedua-dua kumpulan hiperkolesterolemia yang diberi rawatan ekstrak isi dan kulit buah HP sebanyak 43.53% dan 51.36% berbanding tikus kawalan hiperkolesterolemia. Aras TG menunjukkan penurunan secara signifikan (p<0.05) sebanyak 38.0% bagi kumpulan tikus yang diberi rawatan ekstrak isi dan 42.98% bagi rawatan dengan ekstrak kulit buah HP. Peningkatan aras MDA-TBAR hati telah direncat dengan penurunan aras MDA-TBAR sebanyak 56.85% bagi kumpulan tikus yang diberi ekstrak kulit serta sedikit penurunan iaitu 10.27% bagi tikus yang diberi ekstrak isi berbanding tikus kawalan hiperkolesterolemia. Kajian ini menunjukkan bahawa kedua-dua ekstrak akues isi dan kulit buah HP merendahkan aras lipid serum serta aras MDA-TBAR hati pada tikus teraruh hiperkolesterolemia. Walau bagaimanapun, kesan ekstrak kulit lebih jelas berbanding ekstrak isi yang mungkin disebabkan oleh kandungan betasianin yang lebih tinggi dalam kulit berbanding isi buah HP.
Estrogen replacement therapy (ERT) is the main treatment postmenopausal osteoporosis. However, ERT causes serious side effects, such as cancers and thromboembolic problems. Labisia pumila var. alata (LPva) is a herb with potential as an alternative to ERT to prevent complications of osteoporosis, especially fragility fractures. This study was conducted to determine the effects of LPva on the biomechanical strength of femora exposed to osteoporosis due to estrogen deficiency, using the postmenopausal rat model. Thirty-two female rats were randomly divided into four groups: Sham-operated (Sham), ovariectomized control (OVXC), ovariectomized with Labisia pumila var. alata (LP), and ovariectomized with ERT (Premarin) (ERT). The LPva and ERT were administered via oral gavage daily at doses of 17.5 mg/kg and 64.5 μg/kg, respectively. Following two months of treatment, the rats were euthanized, and their right femora were prepared for bone biomechanical testing. The results showed that ovariectomy compromised the femoral strength, while LPva supplementation to the ovariectomized rats improved the femoral strength. Therefore, LPva may be as effective as ERT in preventing fractures due to estrogen-deficient osteoporosis.
Statins are HMGCoA reductase inhibitors and had been demonstrated to stimulate bone formation in rodents after high oral doses. Observational studies on patients treated with oral statins were varied. Delta-tocotrienol had been found to stimulate the cleavage of HMGCoA reductase and inhibit its activity. Tocotrienols were found to have both catabolic and anabolic effects on bone in different animal models of osteoporosis. The current study aimed to ascertain the effects of delta-tocotrienol and lovastatin combination on biochemical and static bone histomorphometric parameters in a postmenopausal rat model at clinically tolerable doses. 48 Sprague Dawley female rats were randomly divided into 6 groups: (1) baseline control group; (2) sham-operated control group; (3) ovariectomised control group; (4) ovariectomised and 11 mg/kg lovastatin; (5) ovariectomised and 60 mg/kg delta-tocotrienol; (6) ovariectomised and 60 mg/kg delta-tocotrienol + 11 mg/kg lovastatin. These treatments were given daily via oral gavage for 8 weeks. Delta-tocotrienol plus lovastatin treatment significantly increased bone formation and reduced bone resorption compared to the other groups. Therefore, the combined treatment may have synergistic or additive effects and have the potential to be used as an antiosteoporotic agent in patients who are at risk of both osteoporosis and hypercholesterolemia, especially in postmenopausal women.
Lignosus rhinocerus (L. rhinocerus), which is known locally as Tiger Milk mushroom, is traditionally used in the treatment of asthma by indigenous communities in Malaysia. However, to date, its efficacy on asthma has not been confirmed by scientific studies and there is also sparse information available on its active constituents. In this study, the volatile constituent of L. rhinocerus hot water extract was investigated using gas chromatography mass spectrometry (GC-MS). The potential effects of L. rhinocerus extract for anti-asthmatic activity was further investigated on ovalbumin (OVA)-sensitized asthmatic Sprague Dawley rats.
Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days). Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardized methanolic extract of ketum (SMEMS) in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for hematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.