This in-vivo experimental study examined the potential effects of AT on Cdcl2-induced kidney toxicity in rat. Our results showed that administration of Cdcl2 significantly increased MDA levels, and decreased the enzymatic and non-enzymatic antioxidants in the kidney of rats. Similarly, Renugadevi et al.(Renugadevi and Prabu, 2009) suggested oxidative stress as the main mechanism of acute Cd toxicity. Prior studies reported significant increased MDA levels in the kidney from CdCl2 -administered rats.(Gabr et al., 2019; Mohammed and Hashem, 2019) In addition, Mohammed et al.(Mohammed and Hashem, 2019) reported that CdCl2 (5 mg/kg/day) orally for 30 days significantly increased MDA, lowered activity of GSH and histopathological changes in the rat. Our results suggest that CdCl2 administration resulted in the reduction of renal GSH concentration as compared to control group, which is in agreement with the previous results obtained by Xiao,(Xiao et al., 2002) and Messaoudi et al.(Messaoudi et al., 2009) Indeed, these findings agreed with previous study on cadmium in male jewelry manufacturing workers, indicated decrease in plasma antioxidant enzymes, and increase in MDA and erythrocyte instability.(Moitra et al., 2014)
Our results showed the administration of CdCl2 significantly decreased GPx (doses of 2 and3 mg/kg), SOD, and GSH (dose of 3 mg/kg ) activities in the kidney compared to a control group and resulted in oxidative stress in the rat kidney that was reflected by the renal histopathological and biochemical changes. Our results were in agreement with a rat experimental study by Adi et al.(Adi et al., 2016) concluded that Cd exposure (20 mg/kg bodyweight for 30 days) meaningfully reduced CAT, GR, SOD, and GPx activities and improved LPx and GST activities. Also, Hormozi et al.(Hormozi et al., 2018) demonstrated that concurrent workplace exposure to lead and cadmium in tile industry might result in a remarkable increase in lipid peroxidation, and altered antioxidant enzymes (CAT, SOD, and GPx) and oxidative stress.
In our study, the functional nephrotoxicity was indexed through BUN and creatinine levels, which were increased in CdCl2-treated rats as matched to control rats. Our results confirm the study by Wallin et al.(Wallin et al., 2014) revealed a link between Cd levels in urine and blood with exposure to Cd and chronic kidney disease. Our findings also correlated with the results of Andjelkovic et al.(Andjelkovic et al., 2019) that suggested Cd (15 and 30 mg/kg BW) significantly increased BUN and Cr compared to a control group Cdcl2- induced oxidative stress in rat kidney. Another study showed that BUN and serum creatinine levels significantly reduced following administration of CdCl2 (25 mg/kg, orally for 7 days) in rat.(Kim et al., 2018) Previous studies have shown severe histological changes in the kidney of CdCl2-treated rats.(Gabr et al., 2019; Mohammed and Hashem, 2019) Besides, CdCl2 exposure induced toxic injuries to the renal and declined glomerular function and progressive renal failure in the kidney, as seen by histopathological examination of the current study and as reported before by Gabr,(Gabr et al., 2019) Renugadevi,(Renugadevi and Prabu, 2009) and Mohammed et al.(Mohammed and Hashem, 2019)
Our experiment revealed that the pretreatment of AT before CdCl2 poisoning improved biochemical parameters. Previous study showed protective effect of AT on antioxidant enzymes and inhibits the reduction of endogenous antioxidant enzymes.(Ozbek et al., 2009) In this study, taking AT (20 mg/kg/day) plus CdCl2 did have much biochemical and pathological impact in rat kidney. However, conflicting results have been reported regarding the effect of AT on renal tissue. Some studies find the effect toxic and others find it useful and supportive.(Mehrzadi et al., 2016; Nasri et al., 2016) Mehany et al.(Mehany et al., 2013) reported the effect of pretreatment with AT and vitamin E on rat's kidney. They suggested that in potassium dichromate-induced nephrotoxicity (15 mg/kg) in rat, pretreatment with vitamin E (200 mg/k) and Atorvastatin (10 mg/kg/day for 14 days) resulted in lowered toxicity and as well as improvement of kidney histopathological changes. In another study, Talebpour et al.(Talebpour Amiri et al., 2018) reported that AT administration produced a significant protective effect against radiation-induced nephrotoxicity.
A study reported opposite results showed that administration of AT (30 mg/kg/day for 8 weeks) induced adverse effect in renal tissues and a post-treatment of Arjunolic acid (20 mg/kg for 4 days) and vitamin C might protect kidney from AT-induced severe tissue toxicity.(Pal et al., 2015) Three major differences between our findings and the results of Pal et al.(Pal et al., 2015) could be due to the discrepancy between dose, exposure time, and animals. In the current study, rats were exposed to 20 mg/kg AT for 15 days, while in Pal et al.(Pal et al., 2015) study mice were given 30 mg/kg/day AT for 8 weeks.
Our results highlighted that the administration of CdCl2 in rat model may lead to nephrotoxicity. Histological examination showed many alterations in renal tissue structure following exposure to CdCl2 (Fig. 6b). These results consistent with those of Mohammad et al.(Mohammed and Hashem, 2019) which described CdCl2 (5 mg/kg b.w, orally for 4 weeks) induced glomerular injury, acute dilatation of Bauman’s capsule, congestion of the renal blood vessels, and injury to glomerular epithelial in rat.
A previous report concluded that CdCl2 administration (5 mg/kg for 30 days) indicated adverse effect on cortical blood flow and renal parenchyma replacement with numerous lymphocytes infiltrates, and dilation of glomeruli in rat.(Gabr et al., 2019) Also, El-Sokkary et al.(El-Sokkary et al., 2010) who reported that CdCl2 (5-mg /kg b.w for 22 days) are associated with spaces separating the cortical tissue, attributed to the cellular degeneration and interstitial edema, mesangial cell proliferative glomerulonephritis in rat, and dilation of Bowman's spaces.
Our results indicated that in cadmium-induced nephrotoxicity pretreatment of AT (20 mg/kg/day) significantly improved concentrations of SOD, GSH and GPx in rat kidney and significantly decreased MDA, BUN, and Creatinine contents. The results of this study confirm previous studies, suggesting the antioxidant effect of AT. (Ghelani et al., 2019; Ozbek et al., 2009) Additionally, our findings suggest that the administration of AT might reduce cadmium-induced tissue damage. Similar to our findings El-Moselhy et al.(El-Moselhy and El-Sheikh, 2014) showed AT intake (10 mg/kg for 10 days) produced a renal protective effect against doxorubicin (15mg/kg for 5 days) induced nephrotoxicity.