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. 2022 Sep 30:2022:8739815.
doi: 10.1155/2022/8739815. eCollection 2022.

The Preventive Effects of Naringin and Naringenin against Paclitaxel-Induced Nephrotoxicity and Cardiotoxicity in Male Wistar Rats

Shimaa S Khaled  1 , Hanan A Soliman  1 , Mohammed Abdel-Gabbar  1 , Noha A Ahmed  2 , Kandil Abdel Hai Ali Attia  3 , Hesham A Mahran  4   5 , El-Shaymaa El-Nahass  6 , Osama M Ahmed  2
Affiliations

The Preventive Effects of Naringin and Naringenin against Paclitaxel-Induced Nephrotoxicity and Cardiotoxicity in Male Wistar Rats

Shimaa S Khaled et al. Evid Based Complement Alternat Med. .

Abstract

This study assessed the preventive properties of naringin and naringenin on paclitaxel-induced nephrotoxicity and cardiotoxicity in adult male Wistar rats. Intraperitoneal injection of paclitaxel 2 mg/kg body weight, two days/week on the 2nd and 5th days of each week, with or without oral administration of naringin and/or naringenin 10 mg/kg body weight every other day, was continued for six weeks. Treatment of rats with naringin and/or naringenin significantly reversed elevated serum creatinine, urea, and uric acid levels caused by paclitaxel, reflecting improved kidney function. Similarly, heart dysfunction induced by paclitaxel was alleviated after treatment with naringin and/or naringenin, as evidenced by significant decreases in elevated CK-MB and LDH activities. After drug administration, histopathological findings and lesion scores in the kidneys and heart were markedly decreased by naringin and/or naringenin. Moreover, the treatments reversed renal and cardiac lipid peroxidation and the negative impacts on antioxidant defenses via raising GSH, SOD, and GPx. The preventive effects of naringin and naringenin were associated with suppressing oxidative stress and reestablishing antioxidant defenses. A combination of naringin and naringenin was the most efficacious in rescuing organ function and structure.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Photomicrographs of kidney sections of different experimental groups. (a) A photomicrograph of a kidney segment of healthy rats revealed glomeruli (G), proximal tubules (PTs), and distal tubules (DTs) and all had typical histologic structures. (b) A photomicrograph of the kidney section of paclitaxel-administered rats passing through the blood vessel (BV) underwent significant degenerative changes (DCs) that were linked with localized mononuclear leukocyte infiltration (IC). (c) Another kidney section of paclitaxel-administered rats revealed the presence of severe apoptotic changes (AP). (d) A photomicrograph of the kidney section of rats given paclitaxel and treated with naringin revealed mild apoptotic changes (AP) and mild degenerative changes (DCs) linked with lymphocytic infiltration (IC). (e) A photomicrograph of the kidney section of rats given paclitaxel and treated with naringenin showing congested glomerulus (CG), mild degenerative changes (DCs), minor apoptotic changes (AP), focal pyknotic nuclei (PN), and significant inflammatory cell infiltration were all visible (IC). (f) A kidney section of rats given paclitaxel and treated with a combination of naringin and naringenin showing infiltration of inflammatory cells (ICs), minor apoptotic changes (AP), and minor degenerative changes (DCs) (H&E; 400X).
Figure 2
Figure 2
Photomicrographs of heart sections of different experimental groups. (a) A section of the rat's normal heart was photographed, revealing the typical histologic anatomy of its cardiac muscles (CM). (b, c) The heart of a paclitaxel-treated rat is shown in a photomicrograph, with marked degenerative changes (DCs), inflammatory cell infiltration (IC), hyalinosis (H), and apoptotic changes (AP). (d) The cardiac tissue of rats given paclitaxel and naringin revealed moderate degenerative changes (DCs) and minor apoptotic changes (AP). (e) Mild hyalinosis (H) was visible in the cardiac section of paclitaxel-administered rats treated with naringenin. (f) A section of the heart of paclitaxel-administered rats treated with a combination of naringin and naringenin revealed moderate degenerative changes (DCs) linked with minimal inflammatory cell infiltration (IC) (H&E; 400X).
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