Nanocurcumin Improves Lipid Status, Oxidative Stress, and Function of the Liver in Aluminium Phosphide-Induced Toxicity: Cellular and Molecular Mechanisms.

Background: The present study aimed to evaluate the effect of nanocurcumin and curcumin on liver transaminases, lipid profile, oxidant and antioxidant system, and pathophysiological changes in aluminium phosphide (ALP) induced hepatoxicity. Material and Methods. In this experimental study, thirty-six male Wistar rats were randomly divided into six groups curcumin (Cur), nanocurcumin (Nanocur), ALP, ALP+Cur, and ALP+Nanocur. All treatments were performed by oral gavage for seven days. After treatment, animals were sacrificed, and liver and blood samples were taken. Serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), total bilirubin, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were measured by photometric methods. Total antioxidant capacity (TAC) and malondialdehyde (MDA) as parameters of oxidative stress and mRNA expression of the nonenzyme protein including Sirtuin 1 (STR1), Forkhead box protein O1 (FOXO1) and protein O3 (FOXO3), catalase (CAT), and glutathione peroxidase (GPX) as the enzyme protein in homogenized tissues have been investigated. A histologist analyzed liver tissue sections after staining with hematoxylin-eosin. Results: In the aluminium phosphide group, there was a significant increase in MDA, ALT, AST, and AP and total bilirubin, cholesterol, triglyceride, LDL, and VLDL; AST, ALT, total bilirubin, LDL, VLDL, cholesterol, and MDA were significantly decreased; and HDL and TAC were significantly increased compared to ALP (P < 0.05). In the ALP+Nanocur group, ALT, AST, ALP, total bilirubin, cholesterol, LDL, VLDL, triglyceride, and MDA were significantly decreased and HDL and TAC were increased significantly (P < 0.05). The effect of nanocurcumin on controlling serum levels of LDL, VLDL, triglyceride, and MDA in ALP-poisoned rats was significantly more than curcumin (P < 0.05). The ALP group had significant changes in genes SIRT1, FOXO1a, FOXO3a, CAT, and GPX compared to healthy controls (P < 0.05). Nanocurcumin mice expressed more SIRT1, FOXO1a, CAT, and GPX genes than controls, and curcumin-treated mice expressed more SIRT1 and FOXO1a genes (P < 0.05). Histopathological findings also indicated a more significant protective effect of nanocurcumin relative to curcumin against ALP-induced hepatotoxicity. Conclusion: Nanocurcumin significantly protects the liver against aluminum phosphide toxicity. It is suggested that nanocurcumin-based drugs be developed to reduce the toxic effects of ALP in poisoned patients.

Chronic exposure to organophosphate pesticides as an important challenge in promoting reproductive health: A comparative study.

INTRODUCTION: Organophosphate compounds (OPCs) are suspected to make changes in reproductive function by oxidant/antioxidant balance disruption in the brain, consequently impairing hypothalamic, pituitary endocrine functions, and gonadal processes. The aim of this study was to investigate the effects of occupational exposure to OPCs on the reproductive system of farm workers, in Hamadan, Iran. MATERIALS AND METHODS: A comparative study was conducted in rural farmers and urban men aged 20-40 years. After sampling and analysis of semen quality parameters (such as sperm count, sperm motility, progressive sperm motility, and sperm morphology), serum butyrylcholinesterase (BChE) activity (a specific biomarker in OPCs exposure), as well as total antioxidant capacity, nitric oxide, and lipid peroxidation levels for both semen and serum samples were determined. In addition, serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone (LH), and testosterone. RESULTS: Our findings showed that the number of sperms (P = 0.04), their motility (P < 0.001), and progressive status (P < 0.001) in rural farmers were significantly lower than the urban population. In addition, a significant decrease was observed in BChE activity (P < 0.001) and LH level (P < 0.001), and also a remarkable increase was found in testosterone level (P = 0.0014) in the serum of rural farmers compared to the urban population. Along with a decrease in semen total antioxidant capacity, a positive significant correlation was found between sperm motility and semen antioxidant capacity (r = 0.45; P < 0.05). CONCLUSION: Exposure to OPCs may affect reproductive outcomes through impairing hypothalamic and/or pituitary endocrine dysfunctions and gonadal processes in farmers.

Protective effect of amlodipine on diazinon-induced changes on oxidative/antioxidant balance in rat hippocampus.

Oxidative stress (OS) is a main mechanism in organophosphorus poisoning. The effects of calcium channel blockers have been confirmed in decreasing of oxidative stress. In the current study, the effects of amlodipine (AM), as a calcium channel blocker, were evaluated on oxidative damages induced by diazinon (DZN) in hippocampus tissue of Wistar rats. Forty-two rats were divided into six groups and treated intraperitoneally for two weeks. Group 1 served as control received vehicle, group 2 was treated with 9 mg/kg of AM, group 3 (positive control) received DZN (32 mg/kg), Groups 4, 5, and 6 were treated with 3, 6, and 9 mg/kg of AM adjunct with DZN (32 mg/kg), respectively. After 14 days, all the animals were sacrificed under anesthesia and hippocampus tissue and blood samples were collected for biochemical analysis and histopathology experiments. The results showed that DZN caused significant increase in lipid peroxidation (P < 0.001), nitric oxide (P < 0.001) and lactate dehydrogenase (P < 0.001) levels, depletion of total antioxidant capacity (P < 0.01), and structural changes in hippocampus tissues. Following AM administration, a significant improvement was observed in oxidative biomarkers in hippocampus tissues. Additionally, our biochemical findings were related well with histopathological examinations. In conclusion, the data of this study indicated that AM administration may prevent oxidative damages via improving of energy production and preventing of free radical formation in DZN-exposed animals.