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Pituranthos chloranthus Oil as an Antioxidant-Based Adjuvant Therapy against Cisplatin-Induced Nephrotoxicity.

ABSTRACT: The therapeutic outcome of cisplatin is limited due to its adverse side effects in normal tissues. Despite its potent antineoplastic effect, cisplatin is known by a relevant collateral action, for instance, acute renal failure. The aim of this study was to assess the effectiveness of Pituranthos chloranthus (PC) essential oil for contracting cisplatin-induced toxicity, in Balb/c mice. The standard mouse model of cisplatin-induced acute kidney injury (AKI), consisting of one intraperitoneal injection of cisplatin (20?mg/kg), was adopted. Mice were pretreated by intraperitoneal administration of PC (5 and 10?mg/Kg b.w) for one week. Cisplatin induced alteration in renal and liver functions, evidenced by increased serum biomarkers levels (creatinine, ALT, and AST). Significant mitigation of cisplatin-induced toxicity was confirmed by lowered levels of serum biomarkers and reduced DNA damage in liver and kidney. PC also restored the alterations in oxidative stress markers and proinflammatory cytokine IFN-? level. Overall, this study provides, for the first time, that PC can be applied as an antioxidant-adjuvant treatment to mitigate cisplatin-induced renal failure.

SUBMITTER: Lahmar A

PROVIDER: S-EPMC7244948 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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<i>Pituranthos chloranthus</i> Oil as an Antioxidant-Based Adjuvant Therapy against Cisplatin-Induced Nephrotoxicity.

Lahmar Aida A Dhaouefi Zaineb Z Khlifi Rihab R Sioud Fairouz F Ghedira Leila Chekir- LC

Journal of toxicology 20200514

The therapeutic outcome of cisplatin is limited due to its adverse side effects in normal tissues. Despite its potent antineoplastic effect, cisplatin is known by a relevant collateral action, for instance, acute renal failure. The aim of this study was to assess the effectiveness of <i>Pituranthos chloranthus</i> (PC) essential oil for contracting cisplatin-induced toxicity, in Balb/c mice. The standard mouse model of cisplatin-induced acute kidney injury (AKI), consisting of one intraperitonea ...[more]

PMID: 32508917

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Project description:Cisplatin is an antineoplastic agent used in the treatment of various types of solid tumors. Despite the dose-dependency of its antineoplastic effect, the high risk for nephrotoxicity frequently precludes the use of higher doses. ?-Linolenic acid (ALA), a carboxylic acid having three cis double bonds, is an essential fatty acid required for health and can be acquired via foods that contain ALA or supplementation of foods high in ALA. Previous studies have shown that ALA demonstrates anti-cancer, anti-inflammatory, and anti-oxidative effects. In this study, we show the protective effect of ALA on cisplatin-induced renal toxicity associated with oxidative stress in mice using biochemical parameters. The mice were randomly assigned into four experimental groups. Group 1 (control group) were administered physiological saline solution for 9 days; group 2 (ALA group) received 200 mg/kg alpha-linolenic acid via gavage for 9 days; group 3 (CIS group) received 100 mg/kg intraperitoneal (i.p.) CIS for 9 days; and group 4 (ALA?+?CIS group) received 100 mg/kg i.p. CIS and followed by ALA 200 mg/kg via gavage for 9 days. Alpha-linolenic acid significantly reduced the expression of myeloperoxidase (MPO), phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the ALA?+?CIS group compared to the CIS group. Furthermore, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) quantities were significantly elevated in the ALA?+?CIS group when compared to the CIS group. ALA significantly decreased the levels of Bax and cleaved caspase-3, while significantly increasing the level of bcl-2, an anti-apoptotic protein, in the ALA?+?CIS group than in the CIS group. Finally, histopathological examination in renal tissue showed that the significant edematous damage induced by CIS administration alone was reduced in ALA?+?CIS group. In conclusion, our findings show that ALA is beneficial to CIS-induced nephrotoxicity in mice via its anti-inflammatory and anti-oxidative effects.

Dataset Information

Pituranthos chloranthus Oil as an Antioxidant-Based Adjuvant Therapy against Cisplatin-Induced Nephrotoxicity.

Publications

<i>Pituranthos chloranthus</i> Oil as an Antioxidant-Based Adjuvant Therapy against Cisplatin-Induced Nephrotoxicity.

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