Ameliorative Effect of Coenzyme Q10 and/or Candesartan on Carboplatin-Induced Nephrotoxicity: Roles of Apoptosis, Transforming Growth Factor-Β1, Nuclear Factor Kappa-B And The Nrf2/HO-1 Pathway

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Carboplatin is a drug that is used for treatment of many types of cancer. However, it may produce </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">serious nephrotoxicity. Candesartan is angiotensin II receptor antagonist employed mainly for control of hypertension. </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Coenzyme Q10 (CoQ10) is a fat-soluble substance which was proven to have potent antioxidant and anti-inflammatory </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">properties. </span></span><strong><span style="font-size: small;">Aim: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Our aim was to study the effects of candesartan and/or CoQ10 on carboplatin-induced nephrotoxicity in mice. </span></span><strong><span style="font-size: small;">Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Sixty mice were divided into 6 equal groups: Control untreated; carboplatin; carboplatin + candesartan; carboplatin + CoQ10; carboplatin + carboxymethyl cellulose; and carboplatin + candesartan + CoQ10 group. Kidney weight/body weight ratio, blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-D-glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT) and the urinary albumin excretion rate (UAER) were determined. Renal tissue catalase (CAT), glutathione reductase (GR), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">oxygenase-1 (HO-1), transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α) and interleukin </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">6 (IL-6) were also determined, along with mitochondrial complex I activity. In addition, portions of the kidney were subjected to histopathological and immunohistochemical examination. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Candesartan and/or CoQ10 induced </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">significant improvement of renal and mitochondrial functions with significant increase in tissue CAT, GR, Nrf2 and HO-1 content associated with significant decrease in the kidney weight/body weight ratio, tissue TGF-β1, TNF-α and </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">IL-6 and alleviation of the histopathological and immunohistochemical changes as compared to carboplatin alone </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">group. These effects were more significant in candesartan/CoQ10 combination group compared to either candesartan </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">or CoQ10 alone. </span></span><strong><span style="font-size: small;">Conclusion: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Candesartan/CoQ10 combination might represent a beneficial therapeutic modality for </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">amelioration of carboplatin-induced nephrotoxicity. </span></span>