ABSTRACT
Background: Hypertension is associated with cardiovascular dysfunction, dysregulation of the antioxidant system and alteration of the level of some enzymes in the metabolic pathway. The possible modulatory effect of acute renal denervation (ARD) on cardiovascular function and the antioxidant system is still a subject of intense debate. This study sought to ascertain the ameliorative effects of ARD on cardiovascular parameters, antioxidant system, creatine kinase and lactate dehydrogenase levels. Methods: Thirty-six Sprague-Dawley rats (5-6 weeks old) were divided into 6 groups of 6 animals each consisting of Normal Salt, High Salt, Normal Salt + Sham Denervation, High Salt + Sham Denervation, Normal Salt + Renal Denervation and High Salt + Renal Denervation. Induction of hypertension with 8 % salt in the diet lasted for 8 weeks. Renal or Sham denervation was thereafter done on selected groups. At the end of the experimental period, cardiovascular parameters, plasma antioxidant status, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) levels were assessed. Significance level was set at p < 0.05. Results: Salt-loading significantly increased systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), rate pressure product (RPP) while reducing superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT). Acute renal denervation significantly (p < 0.0001) reduced SBP, DBP, MABP, RPP, LDH and norepinephrine level while increasing SOD, GSH and CAT. ARD did not significantly alter CK level. Conclusion: Acute renal denervation, by reducing sympathetic activity, ameliorates cardiovascular and antioxidant functions as well as reduces LDH level without significantly altering CK level in salt-induced hypertension.
ABSTRACT
BACKGROUND: Cisplatin is an anti-cancer drug that causes nephrotoxicity and oxidative stress. Extracts of Nigella sativa is nephroprotective. Vitamin E is also a potent antioxidant. This study sought to determine a possible synergistic effect of administering the two agents prior to cisplatin use on nephrotoxicity and oxidative stress. METHODS: 48 male Wistar rats were randomly divided into 6 groups of 8 rats each. Group I served as the control. Group II received cisplatin without any treatment for 6 days. Groups III, IV, V and VI received 100 mg/kg Nigella sativa (NS), 200 mg/kg NS, 100 mg/kg Vitamin E and 200 mg/kg NS+100 mg/kg Vitamin E respectively for 5 days prior to 6 days administration of cisplatin. On the last day of the experiment, all the animals were sacrificed and serum samples collected for analysis. RESULTS: Cisplatin administration caused a significant increase in creatinine level (p<0.01), urea level (p<0.01), sodium concentration and malondialdehyde level (p<0.001). Pre-administration with NS caused a significant reduction in creatinine level (p<0.001), urea level (p<0.001), sodium concentration (p<0.001) and malondialdehyde (p<0.01) level. Pre-administration with vitamin E caused a significant reduction in creatinine level (p<0.001), urea level (p<0.01), sodium concentration (p<0.001) and malondialdehyde level. They both also caused a significant increase in superoxide dismutase, reduced glutathione and catalase (CAT) levels. The combination of NS and vitamin E however did not show significant synergistic effects. CONCLUSION: These results suggest that even though pre-administration of the two agents protect against renal toxicity and oxidative stress, the effects are however not collaborative.
