Results Of Subchronic Toxicity Study Research Articles

Acute and subchronic toxicity as well as evaluation of safety pharmacology of modified pulsatilla granules

The present study investigated acute and subchronic toxicity and safety pharmacology of modified pulsatilla granules (MPG) to provide a basis for a comprehensive understanding of MPG toxicity. The results of acute toxicity testing showed that the median lethal dose of MPG was more than 5000 mg kg−1, suggesting that MPG was considered as practically non-toxic. The subchronic toxicity study for 30 days was conducted by daily oral administration at doses of 375, 750 and 1 500 mg kg−1 in Sprague-Dawley rats. The results of subchronic toxicity study showed that the body weight and relative organ weight were not significantly changed by administration of MPG. The clinical chemistry study showed that MPG could induce kidney and liver damages. In histopathological, mild lesions in liver and kidney were also observed, suggesting that the liver and kidney might be potential target organs of MPG. In the safety pharmacology study, MPG did not exhibited any side effects to rats in cardiovascular system, respiratory system and central nervous system. These results suggested that MPG could be considered safe for veterinary use.

Hepato-renal toxicological studies of ethyl acetate leaf extract of <i>Vitex simplicifolia</i> in wistar rats

This study evaluated the hepato-renal toxicological indices following 21 days administration of ethyl acetate leaf extract of Vitex simplicifolia in Wistar rats. Acute toxicity studies with very high concentrations of the crude extract was carried out followed by sub chronic toxicities studies involving administration of 250mg/kg, 500mg/kg and 1000mg/kg body weight of the ethyl acetate extract to the experimental animals for 21 days. Liver and Kidney toxicological indices were evaluated from the sera as well as e tissues of the experimental animals after the 21 days period of administration. The results of acute toxicity studies indicate that this extract is well tolerated at doses as high as 5000mg/kg body weight. The results of sub-chronic toxicity studies indicate that there was a significant increase in the activities of ALP , while AST activities was significantly lower (p<0.05) compared to the control. There was no significant changes in (P<0.05) ALT and Unconjugated bilirubin levels in the test groups compared to the control. Similarly, the result of kidney toxicological indices showed that the levels of urea, Na+, HCO32- and Cl- were significantly higher in the test animals compared to the control while K+ and creatine levels showed no significant change in the extract administered groups compared to the control (p<0.05). Histopathology examination of the liver and kidneys showed mild hepatic damage at the highest dose (1000mg/kg body weight).Keywords: Vitex simplicifolia, Hepato-renal, Toxicological Studies.

Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability

Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested.

Safety assessment of saponins extract in Dolichos falcatus Klein: Subchronic study in Sprague-Dawley rats

Ethnopharmacological relevanceDolichos falcatus Klein (DF), a Chinese Dai ethnic medicine popularly known as “Tuoyeteng” in Yunnan province of China, has been widely used in China to treat fracture, rheumatoid arthritis and soft tissue injuries for a long time. Our previous study showed that saponins in DF (DFS) ameliorated the gouty arthritis induced by MSU crystals in vivo and in vitro. The present study was carried out to evaluate the no-observed-adverse-effect level (NOAEL) of DFS. Materials and methodsSprague-Dawley rats (10/sex/group) were gavaged with DFS at dose level of 0, 50, 100 and 200mg/kg body weight /day for 90-days. ResultsDFS administration did not result in mortality or show treatment-related changes in clinical signs of toxicity, body weights gain or feed consumption. Similarly, in addition to slightly hemolytic anemia and gastrointestinal tract lesion in males of high-dose treatment group, no toxicologically significant treatment-related changes in hematological, clinical chemistry, urine analysis parameters, organ weights, and macroscopic and microscopic abnormalities were noted during the testing period. ConclusionThe results of subchronic toxicity study support the NOAEL for DFS as 200mg/kg/d in females and as 100mg/kg/d in males. These results provide an important reference for further DFS-related clinical trials or new drug exploration.

Toxicologic evaluation of Dichrostachys glomerata extract: Subchronic study in rats and genotoxicity tests

In western Cameroon, edible fruits and seeds from the plant Dichrostachys glomerata are commonly used as spices. Extract from the fruit pods has been reported as a good natural source of antioxidants and may provide health benefits. The objective of the present study was to investigate potential adverse effects, if any, of D. glomerata fruit pod extract (Dyglomera™) in a subchronic toxicity study and in genotoxicity studies. In the toxicity study, Sprague Dawley rats (20/sex/group) were gavaged with D. glomerata extract at dose levels of 0, 100, 1000 and 2500mg/kg body weight (bw)/day for 90-days. Dyglomera™ administration did not result in mortality or show treatmentrelated changes in clinical signs of toxicity, body weights, body weight gain or feed consumption. Similarly, no toxicologically significant treatment-related changes in hematological, clinical chemistry, urine analysis parameters, and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. Mutagenic and clastogenic potentials as evaluated by Ames assay, in vitro and in vivo chromosomal aberration test and in vivo micronucleus test did not reveal any genotoxicity of the extract. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for D. glomerata extract as 2500mg/kg bw/day, the highest dose tested.

Subchronic toxicity and mutagenicity/genotoxicity studies of Irvingia gabonensis extract (IGOB131)

African Bush Mango from Irvingia gabonensis is a West African culinary fruit and the mucilage from this fruit seed is used to make traditional soups and sauces. Extract from the kernel (IGOB131) has been claimed for its health benefits. In the present investigations, potential adverse effects, if any, of IGOB131 were investigated in dose–response 90-day study and genotoxicity studies. In the subchronic study, Sprague Dawley rats (20/sex/group) were gavaged with I. gabonensis extract (IGOB131) at dose levels of 0, 100, 1000 and 2500mg/kg body weight (bw)/day for 90-days. No treatment-related changes in clinical signs, functional observations, mortality, ophthalmologic observations, body weights, body weight gain or feed consumption were noted. Similarly, hematological, clinical chemistry, urine analysis parameters, and organ weights did not reveal any toxicologically significant treatment-related changes. No treatment-related macroscopic and microscopic abnormalities were noted at the end of treatment period. The mutagenicity as evaluated by Ames assay, in vitro and in vivo chromosomal aberration test and in vivo micronucleus assay did not reveal any genotoxicity of IGOB131. The results of subchronic toxicity study suggest the no-observed-adverse-effect level (NOAEL) for I. gabonensis extract (IGOB131) as ⩾2500mg/kg bw/day, the highest dose tested.