Volume 23, Issue 2

Background: The efficacy of opioids in neuropathic pain is still controversial. Earlier studies have suggested that N-methyl-D-aspartate (NMDA) receptor binding can be affected by opioids and vice versa. The present study aims to explore the interactions between NMDA and opioid receptors using various combinations of drugs acting on these receptors. Methods: We used an animal model of sciatic nerve ligation to induce neuropathic pain, and a hot-plate test was used to assess pain response. Results: It was observed that NMDA and naloxone increased the pain response. Ketamine reduced the pain response, which was further reduced when ketamine was administered in combination with naloxone, but not with NMDA, thus highlighting the activity of the NMDA receptor system. In addition, morphine was also found to increase latency to hind-paw lick, which was further reduced when given in combination with naloxone. Furthermore, triple drug combinations using ketamine+morphine+naloxone and ketamine+NMDA+naloxone demonstrated some significant interactions at these receptors. Conclusions: Thus, our study establishes that neuropathic pain can probably be overcome using higher doses of opioids, and there exists some intimate relationships between NMDA and opioid systems that lead to pain modulation.

Background: In 2001, the Proceedings of National Academy of Sciences (USA) published a study on the relationship between month of birth and longevity. Subsequent studies revealed differences in month of birth among patients with acute myocardial infarction, a major killer in industrialized countries. The aim of the present study was to analyze month of birth in patients with malignant neoplasms, another major fatal disease. Methods: The study sample consisted of 44,487 patients (22,584 male) diagnosed with a malignant neoplasm at Rabin Medical Center in 1994–2011. The number of patients born in each month of the year was calculated for the whole group and by gender. Student’s t-test was used to compare mean (standard deviation) monthly, quarterly and trimester values. Results: There was a strong trend (p=0.06) for a higher mean number of births in the first trimester of the year than in the second and third trimesters. The difference was significant for male patients (p=0.03) but not female patients (p=0.13–0.15). Conclusions: Patients born in the first trimester of the year are more affected by malignancies, particularly males. The overall monthly birth distribution of oncology patients is in line with the paradigm linking birth month with longevity.

Background: Gabapentin, a structural analog of γ-aminobutyric acid (GABA), is used in the treatment of neuropathic pain in multiple sclerosis. Methods: This study investigated the effect of gabapentin on oxidative stress in a model of brain demyelination evoked by intracerebral injection (i.c.i) of ethidium bromide (10 μL of 0.1%). Rats received saline (control) or gabapentin at 100 or 300 mg/kg orally daily for 10 days prior to injection of ethidium bromide. Rats were euthanized 1 day later, and then the levels of reduced glutathione (GSH), glutathione peroxidase (GPx) activity, lipid peroxidation (malondialdehyde; MDA), nitrite, acetyl cholinesterase (AChE) and paraoxonase activities were assessed in the brain cortex in different treatment groups. Results: Ethidium bromide resulted in increased oxidative stress in the cortex 1 day after its injection. Malondialdehyde increased by 30.2%, whereas GSH decreased by 17.6%. GPx activity was inhibited by 78.6%. Brain nitrite increased by 55.4%, AChE activity decreased by 33.4% and paraoxonase activity decreased by 27.5%. In ethidium bromide treated rats, gabapentin administered at 300 mg/kg increased cortical MDA by 66%. GSH was unaltered by gabapentin, but GPx activity decreased by 54.3% by the higher dose of gabapentin. Nitrite decreased by 21.4% and 29.2% after 100 and 300 mg/kg of gabapentin, respectively. AChE activity increased by 28.6% and 69.3% by 100 and 300 mg/kg of gabapentin, respectively. Paraoxonase activity showed 83.3% and 73% decreases by 100 and 300 mg/kg of gabapentin, respectively. Conclusions: These results suggest that gabapentin increases brain lipid peroxidation and decreases brain antioxidant enzymes in this model of chemical demyelination.

Background: Tenofovir (TFR) is a nucleotide reverse transcriptase inhibitor with activity against human immunodeficiency virus. We studied the effect of TFR administered to Wistar rats on hepatic and renal function markers and the possible modulatory role of vitamin E (Vit E). Methods: The study consists of four groups of six rats each. The first group served as control, the second group received TFR at 50 mg/kg/day for 4 weeks, third group received TFR and Vit E, and the last group received Vit E alone. Results: TFR administration caused a significant (p<0.05) increase in the levels of serum urea, creatinine, urinary glucose, and protein by 65%, 51%, 88%, and 79%, respectively, relative to controls. This was followed by a significant (p<0.05) reduction in creatinine clearance of TFR-treated rats. There were no significant differences (p>0.05) in the activities of serum aminotransferases, γ-glutamyltransferase, and alkaline phosphatase in TRF-treated rats relative to controls. TFR administration caused a marked elevation of malondialdehyde (MDA; index of lipid peroxidation) in the animals. Specifically, serum, hepatic, and renal MDA levels increased by 75%, 90%, and 102%, respectively. TRF-treated rats had significantly (p<0.05) reduced activities of renal catalase, glutathione- S -transferase, and superoxide dismutase. Supplementation of Vit E ameliorated TFR-induced effects by decreasing the levels of MDA and enhancing the activities of renal antioxidative enzymes. The biochemical data were supported by histopathological findings from the slides. Conclusions: TFR increased oxidative stress and altered kidney function markers in the rats, whereas supplementation of Vit E attenuated these effects.

Background: Heavy metals generate free radicals and induce oxidative and nitrosative stress with depletion of antioxidants. In this study, we have evaluated the beneficial effects of α-tocopherol against nickel sulfate exposed testicular dysfunction. Methods: We studied the effect of supplementation of α-tocopherol (10 mg/100 g body weight, i.m.) on nickel sulfate (2.0 mg/100 g body weight, i.p.) induced testicular oxidative and nitrosative stress in Wister strain male albino rats. Serum and testicular nitric oxide, L-ascorbic acid and serum α-tocopherol concentrations were evaluated. We also evaluated sperm count, motility and histopathology of testes. Results: Nickel treated rats showed significantly decreased body weight, testicular somatic index, sperm count, sperm motility, serum and testicular L-ascorbic acid concentration and serum α-tocopherol level as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol produced a remarkable improvement of all the above parameters when compared with treatment with nickel alone. Nickel treated rats also had significantly increased serum and testicular nitric oxide concentrations as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol significantly decreased nitric oxide concentrations in both serum and testes, respectively, as compared to nickel treatment alone. Histopathology of the testes revealed tortuous seminiferous tubules, loss of spermatogenesis process (>75%), congestion and necrosis in nickel sulfate treated rats, whereas rats simultaneously treated with nickel sulfate and α-tocopherol had almost normal seminiferous tubules and near normal spermatogenesis as compared to nickel alone treated rats. Conclusions: Nickel sulfate treatment causes testicular oxidative and nitrosative stress in albino rats, but simultaneous supplementation of α-tocopherol was found to be beneficial in combating against such stresses.

Background: The prevalence of diabetes mellitus (DM) is dramatically increasing worldwide. Prospective studies have reported that high levels of hepatic enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) are associated with later development of diabetes. The aim of the present study was to examine the effect of hydroalcoholic extract of Allium hirtifolium (Persian shallot) on the level of liver enzymes in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-two male rats were divided into four groups of eight. The diabetic groups received 100 and 300 mg/kg Persian shallot extract, the diabetic control and non-diabetic control groups received 0.9% saline for 30 days. At the end of the experimental period, fasting blood samples were collected, and enzymes levels were measured. Results: Our findings showed that hydroalcoholic extract of Persian shallot can significantly decrease serum levels of liver enzymes (AST, ALT, ALP and LDH) in treated groups in a dose-dependent fashion (p<0.05). Conclusions: Antioxidant micronutrients in the extract of Persian shallot may rehabilitate liver damages caused by free radicals in diabetic rats.

Background : Nevirapine (NVP) is an antiretroviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in the blood. This study was undertaken to investigate the effect of chronic administration of NVP on body weight, food, and water intake using apparently healthy albino Wistar rats. Methods : Twenty adult albino Wistar rats (50–125 g body weight) were used for the study. Rats in the control group (n=10) were fed normal rodent chow, whereas the NVP group (n=10) were fed by gavage NVP (0.4 mg/kg body weight) two times daily (07.00 h and 18.00 h) in addition to normal rodent chow for 12 weeks. All animals were allowed free access to clean drinking water. Results : Results showed that the mean daily food and water intake in the NVP group were significantly higher (p<0.001) when compared with the control group, respectively. The mean change in body weight in the NVP group was significantly higher (p<0.001) than the control group. Conclusions : These results suggest that chronic administration of NVP may increase body weight in rats, probably due to its stimulatory effects on food and water intake.