Background and purpose: Opiates are traditionally used for the treatment of pain. Chronic consumption of opiates such as morphine (MOR) induces tolerance and dependence. This study aimed to investigate the effects of valsartan (VAL), as an angiotensin II receptor blocker, on the induction and expression of MOR analgesic tolerance and physical dependence in rats. Experimental approach: MOR 10 mg/kg was injected s. c. twice a day for 7 days to induce tolerance and dependence. For evaluating the effect of VAL on the induction of MOR analgesic tolerance and physical dependence, 20 mg/kg VAL was administered orally (once a day) during the 7 days of the examination period. The tail-flick test was performed every day. On day 7, 5 mg/kg naloxone () was injected s. c. into the morphinedependent rats and the rats were monitored for 30 min for the frequency of withdrawal signs such as jumping, diarrhea, defecation, head tremor, rearing, scratching, sniffing, teeth chattering, and wet-dog shake. For evaluating the effect of VAL on the expression of MOR-analgesic tolerance and physical dependence, 45 min before the last MOR injection, VAL was administered only on day 7. The tail-flick test was performed and naloxone was injected into the addicted rats and they were monitored for 30 min for the frequency of withdrawal signs such as jumping, diarrhea, defecation, head tremor, rearing, scratching, sniffing, teeth chattering, and wet-dog shake. Findings/Results: Our results revealed that the co-administration of VAL with MOR for 7 consecutive days reduced the induction of MOR tolerance. Moreover, VAL administration for 7 days along with MOR reduced the frequency of diarrhea and defecation in naloxone-injected animals. Conclusion and implications: According to the results presented in this study, chronic administration of VAL prevented the induction of MOR-analgesic tolerance and dependence in rats.

Objective(s): Doxorubicin (DXR)-induces glomerular atrophy and fibrosis in rat kidneys. The objective of the current study was to investigate the protective effects of valsartan on DXR-induced glomerular toxicity and its mechanisms of actions in rats. Materials and Methods: Male Sprague-Dawley (SD) rats were divided into four groups, and each group contains ten rats. First group was control and was treated with saline only. Treatment groups were injected with DXR (6. 5 mg/kg) alone, or intragastric gavage with 10 mg/kg or 20 mg/kg of valsartan after DXR treatment. Results: Rats treated with DXR only showed significant changes in concentrations of urinary protein, serum creatinine (SCr), and blood urea nitrogen (BUN). Moreover, glomerular structural damages were observed in rats treated with DXR. Valsartan significantly alleviated the effect of DXR. Dramatic elevation in malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS) and significant reductions in the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) were seen after DXR treatment. These effects were effectively ameliorated by coadministration with valsartan. Conclusion: The findings of our study indicate that valsartan may play an important role in protecting DXR-induced renal toxicity, at least in part, through its antioxidant properties.

Introduction: Fetuin-A (A2-HS-glycoprotein) is a protein that plays several functions in human physiology and pathophysiology. The role of fetuin-A in type 1 diabetes mellitus (DM) has been less studied. We investigated the serum levels of fetuin-An in type 1 diabetic patients with microalbuminuria. Furthermore, the blocking effect of renin-angiotensin-aldosteron system on serum levels of fetuin-A was assessed.Materials and Methods:. From January 2010 to May 2011, 32 patients with type 1 DM with confirmed microalbuminuria were included in this study in Isfahan, Iran. Serum fetuin-A levels before and 8 weeks after valsartan administration were measured. In addition, serum lipid profile, creatinine, hemoglobin A1c, and urine microalbuminuria were determined.Results:. The mean age of participants was 21.65 ± 0.38 years. Before valsartan administration, the mean values of fetuin-A were not significantly different between males and females (64.22±1.77 ng/mL versus 61.39±3.35 ng/mL, respectively). After valsartan administration, serum levels of fetuin-A and urine albumin-creatinine significantly decreased. A negative correlation was observed between serum fetuin-A level after valsartan administration and serum low-density lipoprotein cholesterol level (P=.007, r=-0.507).Conclusions:. Administration angiotensin receptor blockers concomitantly decreases fetuin-A levels and urine albumin levels.