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Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis.

ABSTRACT: The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl₂ in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p < 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-?B/PKC-?/TNFR2 activation. In addition, CdCl₂ induced renal fibrosis by triggering TGF-?1/SMAD3/?-SMA/collagen signaling within renal cells. On the other hand, RA significantly (p < 0.05-0.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p < 0.05-0.01) reciprocate Cd-mediated pathological changes in blood and urine parameters in mice. In addition, histological data supported the pharmacological findings. In silico chemometric analyses predicted the possible interactions between RA and different signal proteins and anticipated drug-likeness characteristics of RA. Hence, RA can potentially be applied as a therapeutic agent to treat Cd-mediated nephrotoxicity in future.

SUBMITTER: Joardar S

PROVIDER: S-EPMC6514581 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis.

Joardar Swarnalata S Dewanjee Saikat S Bhowmick Shovonlal S Dua Tarun K TK Das Sonjit S Saha Achintya A De Feo Vincenzo V

International journal of molecular sciences 20190424 8

The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl<sub>2</sub> in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (<i>p</i> < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd ...[more]

PMID: 31022990

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Project description:Cisplatin (Cis) is considered to be one of the most effective drugs for killing cancer cells and remains a first-line chemotherapeutic agent. However, Cis's multiple toxicities (especially nephrotoxicity) have limited its clinical use. Marsdenia tenacissima (Roxb.) Wight et Arn. (MT), a traditional Chinese medicine (TCM) employed extensively in China, not only enhances the antitumor effect in combination with Cis, but is also used for its detoxifying effect, as it reduces the toxic side effects of chemotherapy drugs. The aim of this study was to explore the therapeutic effect of MT on Cis-induced nephrotoxicity, along with its underlying mechanisms. In this study, liquid-mass spectrometry was performed to identify the complex composition of the extracts of MT. In addition, we measured the renal function, antioxidant enzymes, and inflammatory cytokines in mice with Cis-induced nephrotoxicity and conducted renal histology evaluations to assess renal injury. The expressions of the proteins related to antioxidant, anti-inflammatory, and apoptotic markers in renal tissues was detected by Western blotting (WB). MT treatment improved the renal function, decreased the mRNA expression of the inflammatory factors, and increased the antioxidant enzyme activity in mice. A better renal histology was observed after MT treatment. Further, MT inhibited the expression of the phospho-NFκB p65 protein/NFκB p65 protein (p-p65)/p65, phospho-inhibitor of nuclear factor kappa B kinase beta subunit/inhibitor of nuclear factor kappa B kinase beta subunit (p-IKKβ/IKKβ), Bcl-2-associated X (Bax), and Cleaved Caspase 3/Caspase 3 proteins, while the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Recombinant NADH Dehydrogenase, Quinone 1 (NQO1), and B-cell lymphoma-2 (Bcl-2) was increased. The present study showed that MT ameliorated renal injury, which mainly occurs through the regulation of the Nrf2 pathway, the NF-κB pathway, and the suppression of renal tissue apoptosis. It also suggests that MT can be used as an adjuvant to mitigate the nephrotoxicity of Cis chemotherapy.

Dataset Information

Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis.

Publications

Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis.

Similar Datasets

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