Abstract
Carbon tetrachloride (CCl4) is considered an environmental pollutant. Exposure to CCl4 is commonly associated with nephrotoxicity. Objective: The aim of this study was to demonstrate the possible preventive role and underlying mechanism of the single and combined administration of captopril and nigella sativa oil against CCl4 induced nephrotoxicty in male rats. Methods: This study was conducted on sixty four adult healthy male albino rats and divided into 8 groups (8 rats/group). Group I, rats which served as negative control, group II, rats which given liquid paraffin and saline (positive control), groups III, rats which given captopril in a dose of 100 mg/kg daily by gavage (positive control), group IV, rats which given nigella sativa oil in a dose of 4 ml/kg daily by gavage (positive control), group V, rats which injected i.p. with CCl4 three times/ week in a dose of 20 μL/100 gm body weight, group VI, rats which given captopril concurrently with CCl4 in the same mentioned dose and route, group VII, rats which given nigella sativa oil concurrently with CCl4 in the same mentioned dose and route; group VIII, rats which given captopril and nigella sativa oil daily concurrently with CCl4 in the same mentioned dose and route. All rats were given treatment for 6 weeks then sacrificed by decapitation. Biochemical parameters were assessed in all rat groups and statistically analyzed. In addition, histological and immunohistochemical investigations of renal tissues were done. Results: In CCl4 treated rats, the biochemical assays revealed significant statistical increase in the level of serum urea, creatinine, uric acid and nitric oxide as well as increase level of lipid peroxides, reduced glutathione and superoxide dimutase in the kidney tissue. Histological examination showed degeneration of glomeruli and tubules. High immunolabelling for activated caspase-3 in the kidney was detected on immunohistochemical examination. Treatment with captopril and nigella oil singly or in combination with CCl4 resulted in improvement of the biochemical, histological and immunohistological changes and this effect is more evident on their combined administration. Conclusion: Captopril and nigella sativa oil can be used as therapeutic agents in protection against CCl4 induced nephrotoxicity. This effect is attributed to decrease free radicals generation and apoptosis through inhibition of casapse-3 activity in renal tissue. It is recommended to conduct further experimental studies on large numbers and to investigate this effect on nephrotoxic patients.
Highlights
Carbon tetrachloride (CCl4) is an environmental pollutant
Carbon tetrachloride causes cellular damage in the kidney and other tissues such as the liver, heart, lung, testis, brain and blood (Pirinççioğlu et al, 2012). This harmful effect is attributed to oxidative stress that results in generation of free radicals which involved in lipid peroxidation, accumulation of dysfunctional proteins and upregulation of nitric oxide (NO) production (Khan et al, 2009)
Captopril and nigella sativa oil have protective effects against renal damage induced by CCl4
Summary
Carbon tetrachloride (CCl4) is an environmental pollutant. It is one of the aliphatic hydrocarbons that has wide spread uses in different industrial sectors as in production of chlorofluorocarbon refrigerants, foam blowing agents, cleaning compounds and organic solvents industry (Kalaf et al, 2006).Carbon tetrachloride causes cellular damage in the kidney and other tissues such as the liver, heart, lung, testis, brain and blood (Pirinççioğlu et al, 2012).This harmful effect is attributed to oxidative stress that results in generation of free radicals which involved in lipid peroxidation, accumulation of dysfunctional proteins and upregulation of nitric oxide (NO) production (Khan et al, 2009). Carbon tetrachloride (CCl4) is an environmental pollutant. It is one of the aliphatic hydrocarbons that has wide spread uses in different industrial sectors as in production of chlorofluorocarbon refrigerants, foam blowing agents, cleaning compounds and organic solvents industry (Kalaf et al, 2006). Carbon tetrachloride causes cellular damage in the kidney and other tissues such as the liver, heart, lung, testis, brain and blood (Pirinççioğlu et al, 2012). This harmful effect is attributed to oxidative stress that results in generation of free radicals which involved in lipid peroxidation, accumulation of dysfunctional proteins and upregulation of nitric oxide (NO) production (Khan et al, 2009). Free radicals are neutralized by an elaborate antioxidant defense system of enzymes such as glutathione and superoxide dimutase (Abdel Moneim and El-Khadragy, 2013).
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