Restorative activities of curcuma longa on sildenafil induced nephrotoxicity among male albino rats (Rattus norvegicus)

Abstract

Nephrotoxicity is the leading cause of acute kidney injury worldwide with majority of population affected being of African population as it accounts for 18- 27% of acute kidney injuries managed in hospital set up. Its clinical manifestation includes acute and chronic injuries. Sildenafil is among the drugs postulated to affect the kidneys because it releases active radical scavenger chemicals that damage the renal glomerular, capsules and blood vessels. Curcuma longa commonly known as turmeric is used because of its high levels of antioxidants and anti-inflammatory nature. There is paucity of data on its pharmacokinetics, dynamics and restorative benefits, therefore the main objective of this study was to investigate restorative activities of Curcuma longa on sildenafil induced nephrotoxicity among male albino rats. Specific objectives being; to assess the gross histomorphological and stereological changes on kidneys on administration of sildenafil, to determine the different doses of Curcuma longa required to provide restorative effects in sildenafil induced nephrotoxicity, to evaluate the renal biochemical parameters of BUN and creatinine following administration Curcuma longa on sildenafil toxicity and lastly assess gross histomorphological and stereological changes on kidneys on administration of Curcuma longa in sildenafil nephrotoxicity. The study was a post-test only true experimental design, conducted at Maseno University in Kisumu County, Kenya. A total of 25 male albino rats of the species Rattus norvegicus were used and grouped into two groups as control or experimental. The experimental groups were subjected to sildenafil then Curcuma longa respectively at calculated doses. The ethical approval was sought from both the school of postgraduate research committee and animal research committee. Data was entered into excel spread sheet, analyzed using the statistical package for social sciences version 22.0. The kidney biochemical markers were compared before and after restoration using t-Test. One way ANOVA with post hoc Bonferroni was used and a P value ≤0.05 was considered significant. The mean body weight of rats in SIN group was statistically significant(P=0.0001) as compared to Control group and experimental groups. The mean weight of right kidney was slightly higher than left kidney in SIN group although their weight respectively was statistically significant (P=0.0001) as compared to control and experimental groups. The mean volume of right and left kidney in SIN group was statistically significant as compared to control and experimental group. The mean length and thickness in SIN group were statistically significant (P=0.0001) as compared to control and experimental groups. On histological changes in SIN group; the glomerulus was shrunk, bowman`s space dilated, proximal convoluted tubule dilated and epithelial cells appeared necrotic. In experimental groups, medium and high Curcuma longa; the glomerulus appeared normal, bowman`s space narrow, proximal convoluted tubule constricted and epithelial cells were normal and appeared cuboidal in shape. On stereological findings in SIN group; the absolute glomerulus volume was statistically significant (P=0.0001) as compared to control and experimental groups whereas the number weighted volume fraction of epithelial cell was statistically significant (P=0.0001) in SIN group as compared to control and experimental groups. The renal biochemical parameters in SIN group were statistically significant (P=0.0001) as compared to control group. In conclusion, Sildenafil citrate had toxic effects on kidney as demonstrated by the gross morphometrical, histological and stereological changes. Medium and high Curcuma longa dose were more effective as demystified by the gross morphological, histomorphological and stereological changes. There were no changes in biochemical parameters in SIN group as compared to experimental groups. Medium and high Curcuma longa doses were found to improve the gross morphometrical, histomorphological and stereological changes. Therefore, this research recommends that sildenafil has effects on kidney histoarchitecture when used at high dose or prolonged period of time and should be regulated. Curcuma longa has restorative effects on histoarchitectural changes caused by sildenafil and there is need to do further research to ascertain the pharmacokinetics and pharmacodynamics of the different components responsible for the changes.