Immunotoxicity assessment of sub-chronic oral administration of acetamiprid in Wistar rats.

CONTEXT: Neonicotinoid insecticides are synthetic analogues of nicotine that acts on the central nervous system of insects by blocking post synaptic acetylcholine receptor. Acetamiprid is one of the widely used neonicotinoid class of insecticide used to control sucking insects like aphids, bees, mosquitoes, on crops. Data on the possible immunotoxic nature of acetamiprid are lacking. OBJECTIVE: The present study was conducted in Wistar rats with the objective of evaluating the immunotoxic potential of acetamiprid administered orally at the dose levels of 27.5, 55 and 110 mg/kg b.w. (equivalent to 5.5, 11 and 22 mg/kg b.w.) for a period of 90 days. MATERIALS AND METHODS: In experiment 1, general toxicity testing including the evaluation of clinical signs, hemato-biochemical changes, response of the lymphocytes towards T and B cell mitogens, macrophage function, gross and histopathology of the lymphoid organs (spleen, thymus, lymph nodes, etc.) were performed. In the second experiment, humoral and cell-mediated responses during immunological challenges were evaluated. RESULTS: Significant decreases were observed in the stimulation index of lymphocyte proliferation to B cell mitogen and in the nitrite production of macrophages of rats treated with 110 mg/kg of acetamiprid. Significant decrease in the lymphoproliferative response towards the B cell mitogen indicated the inability of the B lymphocytes to respond on stimulation that might increase the chances of susceptibility to infections. Acetamiprid also caused 15-28% reduction in nitrite production, an important signal for efficient inflammatory response of macrophages. The functional impairment of macrophages may involve aberrations in the enzymatic degradation of microbes, oxidative burst, generation of free radicals, phagocytosis, release of proinflammatory cytokines and thereby, may hamper host defence causing susceptibility to diseases. No significant changes over hematology, biochemistry, organ weights, histopathology of major immune organs, delayed type hypersensitivity test, response to sRBCs and lymphoproliferation assay for T cell mitogen were observed. CONCLUSION: In conclusion, the results demonstrate for the first time that the subchronic administration of acetamiprid (20% SP-soluble powder) cause significant decreases in the lymphocyte proliferation as well as the macrophage function at the dose level of 110 mg/kg. Considering the chronic population adjusted dose (0.023 mg/kg/day) through dietary exposure for acetamiprid, judicious use of acetamiprid is highly essential. Indiscriminate use of acetamiprid exceeding the doses advised might pose a hazard.

Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats.

CONTEXT: Withania somnifera (L) Dunal (Solanaceae) is an important traditional herbal medicine used for thousands of years and is considered as the Indian ginseng. Reports on the effect of Withania somnifera root (WSR) extract on the developing foetus of pregnant rats including mortality, structural abnormalities, changes in growth and effects on dams are not available. OBJECTIVE: The present study was performed to evaluate the prenatal developmental toxicity potential of WSR extract in rats. MATERIALS AND METHODS: WSR extract was given orally to pregnant rats during the period of major organogenesis and histogenesis (days 5 to 19 of gestation) at the dose levels of 500, 1000 and 2000 mg/kg/day. Clinical observations including mortality, moribundity, behavioural changes, signs of overt toxicity, body weight, gross pathological changes of dams and foetal analyses including external malformations, skeletal and soft tissue malformations were evaluated. RESULTS: No evidence of maternal or foetal toxicity was observed. WSR extract caused no changes (p < 0.05) in body weight of parental females, number of corpora lutea, implantations, viable foetuses, external, skeletal and visceral malformations. DISCUSSION AND CONCLUSION: Under the conditions of the study, the no-observed-effect level (NOEL) of WSR extract for maternal and developmental toxicity was concluded to be at least 2000 mg/kg/day.

Formylchromone exhibits salubrious effects against nitrosodiethylamine mediated early hepatocellular carcinogenesis in rats.

The salubrious effects of 3-Formylchromone (3-FC) against nitrosodiethylamine (NDEA) mediated early hepatocellular carcinogenesis was investigated in vivo by this study. Male Wistar rats were administered three interspersed intraperitoneal injections of NDEA (200 mg/kg body weight) until sixth week, followed by, thrice a week oral dose of 3-FC (25 mg/kg body weight) from the seventh week to eleventh week. Oral supplementation of Wistar rats with 3-FC prevented the increase in serum marker enzymes (AST, ALT, LDH) and serum pre-neoplastic marker (γ-GT) induced by NDEA. Biochemical observations were found to be further correlated with histological studies, indicating the potential of 3-FC to mediate suppression of hepatic damage/pre-neoplastic lesions. Argyrophilic nucleolar organizer region (AgNOR) staining was done in histology sections to confirm the anti-proliferative potential of 3-FC against NDEA-induced early hepatocellular carcinogenesis. RT-PCR and immunoblot analysis was done to find the modulations in the gene transcript/protein level expression of pre-neoplastic marker (GST-pi), proliferation marker (PCNA), apoptotic mediators (PPARγ, NFκB-p65 and p53). 3-FC was found to favorably modulate the expressions of GST-pi, PCNA, PPARγ, NFκB-p65, p53 clearly confirming the anti-proliferative and apoptotic potential of 3-FC. Further, the apoptotic effect of 3-FC against NDEA-induced early hepatocellular carcinogenesis was confirmed by caspase-3 activity assay and DNA fragmentation analysis. Based on these findings, it is concluded that 3-FC possesses hepatoprotective, anti-pre-neoplastic, anti-proliferative and apoptosis inducing capability against NDEA-induced early hepatocellular carcinogenesis.

Acute and sub-acute oral toxicity assessment of the hydroalcoholic extract of Withania somnifera roots in Wistar rats.

Withania somnifera is a widely used medicinal plant for several disorders. Toxicity studies on Withania somnifera are not available. Acute and sub-acute oral toxicities of Withania somnifera root extract in Wistar rats were evaluated in the present study. In the acute toxicity study, WSR extract was administered to five rats at 2000 mg/kg, once orally and were observed for 14 days. No toxic signs/mortality were observed. In the sub-acute study, WSR extract was administered once daily for 28 days to rats at 500, 1000 and 2000 mg/kg, orally. No toxic signs/mortality were observed. There were no significant changes (P < 0.05) in the body weights, organ weights and haemato-biochemical parameters in any of the dose levels. No treatment related gross/histopathological lesions were observed. The present investigation demonstrated that the no observed adverse effect level was 2000 mg/kg body weight per day of hydroalcoholic extract of W. somnifera in rats and hence may be considered as non-toxic.