The Protective Effect of L-arginine in Cisplatin-induced Nephrotoxicity in Streptozotocin-induced Diabetic Rats.

BACKGROUND: Cisplatin (CP) is accompanied with a nephrotoxicity. L-arginine (LA) plays an important role in the regulation of renal function. The present study was designed to investigate the protective role of LA supplementation in CP-induced nephrotoxicity in a diabetic rat's model. MATERIALS AND METHODS: Sixteen adult female and male Wistar rats were used and they received a single dose of streptozotocin (STZ) (60 mg/kg i.p.). Diabetic female and male rats were arranged as groups 1-5 and groups 6-10, respectively. Groups 1 and 6 (LA groups) received LA alone. Groups 2 and 7 (CP groups) received CP alone. Groups 3 and 8 (CP + LA [PT] groups) received LA as prophylaxis and then treated with LA and CP. Groups 4 and 9 (CP + LA [T] groups) were treated with LA and CP simultaneously. Groups 5 and 10 (CP + LA [P] groups) received LA as prophylaxis and then treated with CP. RESULTS: The serum creatinine (Cr) level of males in Groups 8 and 9 was significantly increased when compared with LA and CP (P < 0.05), whereas no differences were observed in Cr level in female groups. Blood urea nitrogen/Cr ratio and kidney weight were reduced in all CP-receiving male rats. Such observation was not seen in female rats. Different results related to weight loss were obtained between male and female animals. The kidney tissue damage score in CP + LA (PT) male group was significantly greater than CP group (P < 0.05). CONCLUSION: Our findings indicate that administration of LA in female and male rats has no protective effect on the severity of nephrotoxicity induced by CP in diabetic rats.

Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: interference of AMPK/PGC-1α pathway.

Here, we have investigated the effect of metformin pretreatment in the rat models of global cerebral ischemia. Cerebral ischemia which leads to brain dysfunction is one of the main causes of neurodegeneration and death worldwide. Metformin is used in clinical drug therapy protocols of diabetes. It is suggested that metformin protects cells under hypoxia and ischemia in non-neuronal contexts. Protective effects of metformin may be modulated via activating the AMP activated protein kinase (AMPK). Our results showed that induction of 30 min global cerebral I/R injury using 4-vesseles occlusion model led to significant cell death in the rat brain. Metformin pretreatment (200 mg kg/once/day, p.o., 2 weeks) attenuated apoptotic cell death and induced mitochondrial biogenesis proteins in the ischemic rats, analyzed using histological and Western blot assays. Besides, inhibition of AMPK by compound c showed that metformin resulted in apoptosis attenuation via AMPK activation. Interestingly, AMPK activation was also involved in the induction of mitochondrial biogenesis proteins using metformin, inhibition of AMPK by compound c reversed such effect, further supporting the role of AMPK upstream of mitochondrial biogenesis proteins. In summary, Metformin pretreatment is able to modulate mitochondrial biogenesis and apoptotic cell death pathways through AMPK activation in the context of global cerebral ischemia, conducting the outcome towards neuroprotection.