Genipin attenuates cisplatin-induced nephrotoxicity by counteracting oxidative stress, inflammation, and apoptosis

Mahgoub, Eglal; Kumaraswamy, Shanmugam Muthu; Kader, Kamal Hassan; Venkataraman, Balaji; Ojha, Shreesh; Adeghate, Ernest; Rajesh, Mohanraj

doi:10.1016/j.biopha.2017.07.018

Cited by 46 publications

(26 citation statements)

References 59 publications

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“…cP is known to induce aKi as a result of renal tubular epithelial cell injury. erS-induced apoptosis of tubular epithelium cells serves a pivotal role in the pathogenesis of cP-induced nephrotoxicity (9,36). Therefore, the present study investigated whether dex exerted a renoprotective effect on cP-induced aKi in a rat model by inhibiting erS-mediated apoptosis via the α2ar/Pi3K/aKT pathway.…”

Section: Discussionmentioning

confidence: 96%

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Chai

Zhu

et al. 2020

Mol Med Report

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cisplatin (cP) is an effective antineoplastic agent; however, cP-induced acute kidney injury (aKi) seriously affects the prognosis of patients with cancer. endoplasmic reticulum (er) stress (erS)-induced apoptosis serves a pivotal role in the pathogenesis of cP-induced aKi. dexmedetomidine (dex), a potent α 2 adrenergic agonist, has been reported to exert protective effects against aKi. However, the protective effects of dex against cP-induced aKi and the potential molecular mechanisms remain unknown. in the present study, male Sprague-dawley rats were divided into four groups (n=10/group), as follows: control group; cP group, rats received an intraperitoneal (i.p.) injection of 5 mg/kg cP; dex + cP group, rats received an i.p. injection of 25 µg/kg dex immediately after cP treatment; and dex + cP + atipamezole (atip) group, rats received an i.p. injection of 250 µg/kg atip, an α 2 adrenoreceptor (α 2 ar) antagonist, and then received the same treatment as the dex + cP group. rats were anesthetized and sacrificed 96 h after CP injection. Subsequently, serum blood urea nitrogen (Bun) and serum creatinine (Scr) were analyzed, and kidney samples were collected for analyses. Pathological changes were examined using hematoxylin and eosin staining, and protein expression levels were assessed using western blotting and immunohistochemical staining. in addition, apoptosis was examined using a terminal deoxynucleotidyl transferase duTP nick-end labeling assay. The present results suggested that dex protected against cP-induced aKi by attenuating histological changes in the kidney, serum Bun and Scr production. Furthermore, the expression levels of 78-kda glucose-regulated protein, c/eBP homologous protein and caspase-12, and the apoptotic rate in the kidney were decreased following dex treatment. in addition, the expression levels of phosphorylated (p)-Pi3K and p-aKT in the dex + cP group were significantly increased. Conversely, the renoprotective effects of dex were attenuated following the addition of atip. in conclusion, dex may alleviate cP-induced aKi by attenuating erS-induced apoptosis, at least in part, via the α 2 ar/Pi3K/aKT signaling pathway.

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Section: Discussionmentioning

confidence: 96%

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Chai

Zhu

et al. 2020

Mol Med Report

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“…In line, our results showed that CDDP treatment induced cell death in normal human astrocytes, but when combined with GJ, the cytotoxicity in normal astrocytes were improved while the cytotoxic effect in GBM cells were synergistically increased. In the use of combination with CDDP, a study by Mahgoub et al may also suggest another beneficial use of GJ on a possible CDDP side effect in the kidney [71].…”

Section: Discussionmentioning

confidence: 99%

Gardenia jasminoides Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes

Kim

Hong

et al. 2020

Nutrients

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Gliomas are the most observed primary brain tumor, of which glioblastoma multiform (GBM) shows the highest incidence. Radiotherapy with temozolomide is the standard therapeutic method, but because of side effects, search for alternative therapies is required. Gardenia jasminoides (GJ) is flavonoid abundant with beneficial effects on inflammation, metabolic diseases, and cancers. In this study, we investigated the synergistic combination of GJ and cisplatin (CDDP) in U87MG and U373MG GBM cells. GJ and CDDP both showed cytotoxicity in U87MG cells, however GJ did not affect viability of normal astrocytes while CDDP displayed high toxicity. Cytotoxic effect of GJ and CDDP was related in apoptosis when confirmed by Western blot assays on cleaved caspase-3, caspase-9, and PARP. Moreover, GJ and CDDP showed synergistic combination in cell death of GBM cells, which was further confirmed by Western blot assays of apoptosis factors and also flow cytometry of Annexin V. Analysis on autophagy factors showed that GJ/CDDP combination induced autophagy, and through inhibition of autophagy, we could confirm autophagy is crucial to cytotoxicity of GJ/CDDP in GBM cell lines. The autophagy-mediated apoptosis of GJ/CDDP was dependent on the AKT/mTOR pathway. Overall, our results suggest GJ/CDDP combination as an effective yet safe therapeutic approach to GBMs.

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“…Genipin was also shown to potentiate the cytotoxic effect of chemotherapeutic agents, such as bortezomib, thalidomide, and paclitaxel in U266 cells [ 49 ]. On the other hand, by suppressing oxidative stress and inflammation, genipin can also attenuate cisplatin-induced nephrotoxicity [ 200 ]. In a murine model of cisplatin-induced nephropathy, genipin pre-treatment was shown to alleviate renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1.…”

Section: Drug Potentiationmentioning

confidence: 99%

Plant-Derived Anticancer Agents: Lessons from the Pharmacology of Geniposide and Its Aglycone, Genipin

Habtemariam

Lentini

2018

Biomedicines

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For centuries, plants have been exploited by mankind as sources of numerous cancer chemotherapeutic agents. Good examples of anticancer compounds of clinical significance today include the taxanes (e.g., taxol), vincristine, vinblastine, and the podophyllotoxin analogues that all trace their origin to higher plants. While all these drugs, along with the various other available therapeutic options, brought some relief in cancer management, a real breakthrough or cure has not yet been achieved. This critical review is a reflection on the lessons learnt from decades of research on the iridoid glycoside geniposide and its aglycone, genipin, which are currently used as gold standard reference compounds in cancer studies. Their effects on tumour development (carcinogenesis), cancer cell survival, and death, with particular emphasis on their mechanisms of actions, are discussed. Particular attention is also given to mechanisms related to the dual pro-oxidant and antioxidant effects of these compounds, the mitochondrial mechanism of cancer cell killing through reactive oxygen species (ROS), including that generated through the uncoupling protein-2 (UCP-2), the inflammatory mechanism, and cell cycle regulation. The implications of various studies for the evaluation of glycosidic and aglycone forms of natural products in vitro and in vivo through pharmacokinetic scrutiny are also addressed.

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Genipin attenuates cisplatin-induced nephrotoxicity by counteracting oxidative stress, inflammation, and apoptosis

Cited by 46 publications

References 59 publications

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Gardenia jasminoides Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes

Plant-Derived Anticancer Agents: Lessons from the Pharmacology of Geniposide and Its Aglycone, Genipin

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