Liver tissue changes induced by biological and chemical silver nanoparticles in trained male Wistar rats.

INTRODUCTION: Despite the widespread use of chemical and biological nano-silver are in industry, their side effects on hepatocytes have been less studied. On the other hand, different types of physical activities may increase liver resistance to toxins. Therefore, the aim of this study was to evaluate the resistance of hepatocytes to receiving chemical versus biological silver nanoparticles in aerobic and anaerobic pre-conditioned rats. MATERIALS AND METHODS: 45 male Wistar rats with similar average range of age (8-12 weeks) and weight (180-220 g), were randomly divided normally into 9 groups, including Control (C), Aerobic (A), Anaerobic (AN), Biological nano-silver (BNS), Chemical nano-silver (CNS), Biological nano-silver + Aerobic (BNS+A), Biological nano-silver + Anaerobic (BNS+AN), Chemical nano-silver + Aerobic (CNS+A) and Chemical nano-silver + Anaerobes (CNS+AN). Prior to injection, rats trained on a rodent treadmill, 10 weeks, 3 sessions per week, according to aerobic and anaerobic protocols.Then, 48 h after the last training session, the rats received 10 % of their body weight, chemical and biological nanosilver intraperitoneally. Liver enzymes (ALT, AST, and ALP) and liver tissue were sent to the relevant laboratories for further evaluation. RESULTS: Results showed that the weight of rats in all groups of physical pre-conditioning, decreased comparison to the control and non-exercise groups, and this decrease was much greater in the anaerobic group (p-value=0.045). Also, the distance traveled in the progressive endurance running a test on a rodent treadmill, increased significantly in the training groups compared to the nano-exercise and control groups (p-value=0.001). Also, the results showed that the level of ALT in chemical nano-silver (p-value=0.004) and biological nano-silver (p-value=0.044), increased significantly compared to other groups. Also, histopathological results showed that nano-silver injection affects the structure of the liver of male Wistar rats and causes inflammation, hyperemia and destruction of liver cells, especially in chemical nano-silver. CONCLUSION: The results of the present study showed that chemical silver nanoparticles cause liver damage more than comparison biological ones. Also, physical pre-conditioning increases hepatocyte resistance to toxic nanoparticle doses and aerobic preparation appears to be more effective than anaerobic.

Mitochondrial Transplantation Therapy against Ifosfamide Induced Toxicity on Rat Renal Proximal Tubular Cells.

Mitochondrial dysfunction is a basic mechanism leading to drug nephrotoxicity. Replacement of defective mitochondria with freshly isolated mitochondria is potentially a comprehensive tool to inhibit cytotoxicity induced by ifosfamide on renal proximal tubular cells (RPTCs). We hypothesize that the direct exposure of freshly isolated mitochondria into RPTCs affected by ifosfamide might restore mitochondrial function and reduce cytotoxicity. So, the aim of this study was to assess the protective effect of freshly isolated mitochondrial transplantation against ifosfamide-induced cytotoxicity in RPTCs. Therefore, the suspension of rat RPTCs (106 cells/ml) in Earle's solution with the pH of 7.4 at 37°C was incubated for 2 h after ifosfamide (4 mM) addition. Fresh mitochondria were isolated from the rat kidney and diluted to the needed concentrations at 4°C. The media containing suspended RPTCs was replaced with mitochondrial-supplemented media, which was exposed to cells for 4 hours in flasks-rotating in a water bath at 37°C. Statistical analysis demonstrated that mitochondrial administration reduced cytotoxicity, lipid peroxidation (LPO), reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) collapse, lysosomal membrane damage, extracellular oxidized glutathione (GSSG) level, and caspase-3 activity induced by ifosfamide in rat RPTCs. Moreover, mitochondrial transplantation increased the intracellular reduced glutathione (GSH) level in RPTCs affected by ifosfamide. According to the current study, mitochondrial transplantation is a promising therapeutic method in xenobiotic-caused nephrotoxicity pending successful complementary in vivo and clinical studies.