Protective effect of hydroalcoholic extract of Pistacia vera against gentamicin-induced nephrotoxicity in rats.

PURPOSE: Pistacia vera is a plant of the family Anacardiaceae found in Central and West Asia. P. vera nut (Pistachio) possess multiple pharmacological effects such as antimicrobial, anti-hyperlipidemia, antioxidant and anti-inflammatory. This study is designed to evaluate the protective effect of the hydroalcoholic extract of pistachio on gentamicin-induced nephrotoxicity in rats. METHODS: Nephrotoxicity was induced in rats by intraperitoneal injection of gentamicin (100 mg/kg/day for 7 days). Hydroalcoholic extract of pistachio (10, 50 and 100 mg/kg/p.o) was administered for 7 days. The nephroprotective activity was evaluated by determining creatinine clearance, serum creatinine, urine volume, urine glucose and blood urea nitrogen (BUN) levels. The kidneys were processed for histopathological examinations and all specimens were examined for morphologic parameters involving tubular degeneration, tubular necrosis and tubule interstitial nephritis. RESULTS: Results showed a significant increase in the levels of serum creatinine, urine volume, urine glucose and BUN and decrease of creatinine clearance by gentamicin (GA) administration. Co-administration with pistachio extract showed reduction in the levels of serum creatinine, urine volume, urine glucose and BUN and increase of creatinine clearance in all doses but the most significant alteration was observed in doses of 100 mg/kg. Also, the nephroprotective effect of the GA was confirmed by the histological examination of the kidneys. CONCLUSION: The study revealed the nephroprotective effect of the hydroalcoholic extract of pistachio. These findings suggest that pistachio treatment may attenuate renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in the kidney.

Effects of valsartan on morphine tolerance and dependence in rats.

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 morphine-dependent 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.

Calcium dobesilate prevents cisplatin-induced nephrotoxicity by modulating oxidative and histopathological changes in mice.

Cisplatin is one of the synthetic cancer medicines with nephrotoxicity being one of its major side effects. Past research shows that calcium dobesilate (CaD), as a vascular protective agent in diabetic retinopathy, has antioxidant properties. Thus, this study aims to evaluate the protective effects of CaD in cisplatin-induced nephrotoxicity in mice. A many as 28 mice, in the present experimental research, were randomly distributed into four groups, including control, cisplatin (the intraperitoneal administration of 20 mg/kg cisplatin only on the first day of the experiment), cisplatin + CaD 50 (cisplatin with the oral administration of 50 mg/kg CaD), and cisplatin + CaD 100 (cisplatin with the oral administration of 100 mg/kg CaD). The treated groups received CaD by oral gavage for 4 constitutive days. On the fifth day, the mice were sacrificed, and some biochemical (serum levels of Cr and BUN, renal tissue levels of MDA, and renal activities of SOD and GPx) and pathological parameters were evaluated. Based on the results, there was a significant decrease in the renal SOD and GPx activities; in contrast, there was a significant increase in the BUN, Cr, and renal MDA levels following administering cisplatin. However, the CaD treatment (100 mg/kg) significantly attenuated these alterations. In addition, the kidney's histological examination of kidneys confirmed the nephroprotective effects of CaD. The findings proved the protective impact of CaD on cisplatin-induced nephrotoxicity by an improvement in the oxidative stress factors.

Vitamin B12 Administration Facilitates The Antipsychotic And Pain-Relieving Effects Of Quetiapine, In The Alzheimer Patients With Psychotic Symptoms.

BACKGROUND: Psychotic symptoms in Alzheimer's disease (AD) patients are a problem in medicine. The efficacy of the vitamin B12 on the treatment of the psychotic symptoms of the AD patients in the association with antipsychotic drugs Quetiapine and Risperidone, was evaluated in this Study. METHODS: The effects of vitamin B12 along with two other drugs were studied on the Mini-Mental State Examination (MMSE), Clinical Global Impression (CGI), Brief Psychiatric Rating Scale (BPRS) and pain Visual Analogue Scale (VAS) in 47 AD patients with psychotic symptoms, including 4 groups, psychotic AD patients treated with Risperidone, Risperidone plus vitamin B12, Quetiapine and Quetiapine plus vitamin B12 . RESULTS: The results showed that Quetiapine improved all of the psychotic criteria, while Quetiapine plus vitamin B12 had better results on BPRS after 2 weeks, VAS score and MMSE. Risperidone also improves all of the criteria except MMSE and drug efficacy index, while, vitamin B12 neutralize the effects of the Risperidone on the BPRS, VAS, and severity of illness. CONCLUSION: Due to these results, Quetiapine is the preferred antipsychotics drug and Vitamin B12 plays an effective role in treatment as an adjunct therapy.

Sumatriptan ameliorates renal injury induced by cisplatin in mice.

OBJECTIVES: Cisplatin (Cis) is an anticancer compound, which is used for the treatment of various cancers. Sumatriptan (Suma) is a selective agonist of 5-hydroxytryptamine 1B/1D (5HT1B/1D) receptor, which is prescribed for the management of migraine. It is well-established that Suma has anti-inflammatory and antioxidant properties. We have explored the protective effects of Suma in the mitigation of Cis-induced nephrotoxicity. MATERIALS AND METHODS: The mice received a single IP injection of Cis (20 mg/kg) on the first day of the experiment. Suma treatment (0.1 and 0.3 mg/kg/day, IP) was started on day 1 and continued for 3 consecutive days. RESULTS: Creatinine (Cr), blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were elevated and glutathione peroxidase (GPx) as well as superoxide dismutase (SOD) activities were decreased in Cis-treated mice. Suma (more potently 0.3 mg/kg) reduced Cr, BUN and MDA levels and increased SOD and GPx levels. Suma also reduced the acute renal injury (tubular degeneration, tubular cells vacuolation, tubular necrosis and cast), which corresponded to kidney damage in Cis-treated mice. CONCLUSION: These findings demonstrate that Suma mitigates Cis-induced renal injury by inhibition of oxidative stress and enhancing the antioxidant enzymes activities.

The effect of metformin on morphine analgesic tolerance and dependence in rats.

Opiate tolerance and dependence is a worldwide public health problem and gives a significant burden to society. The aim of this study was to evaluate the effects of metformin (MET) on development and expression of morphine tolerance and dependence in rats. For induction of tolerance, morphine sulfate was injected (10 mg/kg, twice a day, s.c.) for 7 days. Animals received metformin (5 and 50 mg/kg, orally, daily) during the examination period for assessing the development of morphine tolerance and dependence. In order to evaluate the expression of morphine tolerance and dependence, single doses of MET (5 and 50 mg/kg, orally) were administered on day 7. Tail flick test was performed to assess the induction of morphine tolerance. For evaluation of morphine dependence, naloxone-induced jumping (5 mg/kg, s.c.) was monitored. Our results showed that 7 days coadministration of 50 mg/kg of MET significantly reduced the development of morphine analgesic tolerance versus morphine + saline treated rats (P < 0.001). Treatment with 50 mg/kg MET reduced the incidence and frequency of jumping in naloxone injected animals (P < 0.01). It is notable that single dose administration of MET, did not prevent the expression of analgesic tolerance and physical dependence to morphine. Based on these results, it can be concluded that MET attenuates the development of morphine analgesic tolerance and dependence in rats.