Protection from doxorubicin-induced nephrotoxicity by clindamycin: novel antioxidant, anti-inflammatory and anti-apoptotic roles

Ibrahim, Kamilia M.; Mantawy, Eman M.; Elanany, Mona M.; Abdelgawad, Hend S; Khalifa, Nuha M; Hussien, Rada H.; El-Agroudy, Nermeen N.; El‐Demerdash, Ebtehal

doi:10.1007/s00210-019-01782-4

Cited by 30 publications

(25 citation statements)

References 46 publications

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“…In alleviation of DOX toxicity, phytochemicals reduce levels of proinflammatory cytokines via downregulating NF-κB signaling pathway [ 97 ]. Furthermore, apoptotic proteins such as Bax and caspase-3 undergo downregulation, while antiapoptotic factor Bcl-2 demonstrates an increase in expression to ameliorate DOX side effects [ 98 ]. Taking everything into together, studies demonstrate that inflammation, oxidative stress and apoptosis are induced following DOX exposure in normal cells and protective agents possess regulatory effect on aforementioned mechanisms in reducing adverse effects of DOX [ 99 , 100 , 101 , 102 ].…”

Section: Doxorubicin: Cancer Resistance and Side Effectsmentioning

confidence: 99%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

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Section: Doxorubicin: Cancer Resistance and Side Effectsmentioning

confidence: 99%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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Section: Discussionmentioning

confidence: 99%

“…On the other hand, renal oxidative stress, inflammation, apoptosis and fibrosis are the most major damaging mechanisms associated with DOX intoxication 16,19,64 . Induction of DNA double breaks and increased generation of ROS remain the most acceptable mechanisms to explain DOX‐induced nephropathy 2,16 . Indeed, DOX generates high quantities of ROS by several mechanisms, including depleting the cellular antioxidants (ie GSH), inducing mitochondria damage, impairment of the respiratory chain and activation of the iron‐dependent pathway 15,65 .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, DOX generates high quantities of ROS by several mechanisms, including depleting the cellular antioxidants (ie GSH), inducing mitochondria damage, impairment of the respiratory chain and activation of the iron‐dependent pathway 15,65 . Besides, DOX‐induced ROS can increase the production of inflammatory cytokines, by stimulating the activity of the NLRP3 inflammasome and subsequent activation of the NF‐κB, which in turn result in a vicious positive feedback cycle that leads to further production of ROS 16,19,66,67 . Both oxidative stress and inflammation lead to the activation of apoptosis and fibrosis by stimulating several pathways in various renal cells, including TGF‐β1/Smad3, p53, Bax, p38 MPAK, JNK/SAPK and capasase1/3 16,17 …”

Section: Discussionmentioning

confidence: 99%

“…Till now, the precise mechanism by which DOX induces AKI is still unclear. However, the currently available data suggest that increased DNA double‐strand breaks, overproduction of ROS, due to depletion of antioxidants, mitochondria damage and iron‐dependent pathway, as well as cellular inflammation, mediated by the activation of NLRP3 inflammasome and nuclear factor‐kappa beta (NF‐κB), are the major interconnected mechanisms involved in DOX‐induced nephropathy 15‐19 . Among all, it is currently well‐accepted that ROS is the central key player in this process which activates all the other adverse mechanisms 16,18,19 …”

Section: Introductionmentioning

confidence: 99%

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Acylated ghrelin protects against doxorubicin‐induced nephropathy by activating silent information regulator 1

Shati

El‐kott

2021

Basic Clin Pharma Tox

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This study investigated the nephroprotective role of acylated ghrelin (AG) against DOX‐induced nephropathy and examined whether the protection involves silent information regulator 1 (SIRT1). Rats were divided into control, control + AG, DOX, DOX + AG, DOX + AG + [D‐Lys3]‐GHRP‐6 (a ghrelin receptor antagonist), and DOX + AG + EX‐527 (a sirt1 inhibitor). DOX was given over the first 2 weeks. AG (10 ng/kg) and both inhibitors were given as 3 doses/wk for 5 weeks. AG improved the structure and the function of the kidneys; down‐regulated the renal expression of TGF‐β1, collagen 1A1 and α‐SMA; and inhibited the renal collagen deposition in the kidneys of DOX‐treated rats. Concomitantly, it reduced the renal levels of ROS, MDA, TNF‐α, and IL‐6 and protein levels of cytochrome‐c, TGF‐β1, Smad3 and α‐SMA in these rats. In both the control and DOX‐treated rats, AG significantly increased the renal levels of SOD and GSH, decreased the expression of cleaved caspase‐3 and Bax, increased the total levels and the nuclear activity of SIRT1 and reduced the deacetylation of p53, NF‐κB and FOXO‐31. All the effects were abolished by the concurrent administration of EX‐527 and [D‐Lys3]‐GHRP‐6. In conclusion, AG prevents DOX‐induced nephropathy in SIRT1 and GSHRa1‐dependent mechanism.

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Ceratonia siliqua pods (Carob) methanol extract alleviates doxorubicin-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways in rats

Atta

Khattab

et al. 2023

Environ Sci Pollut Res

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Doxorubicin (DOX) is an anti-neoplastic therapy, but its use is limited by its deleterious toxic effects including nephrotoxicity and cardiotoxicity. This work aimed at assessing the potential protective effect of Ceratonia siliqua methanol extract (CME) on DOX-induced nephrotoxicity in 5 groups of Wistar rats. Nephrotoxicity was induced experimentally by intraperitoneal (IP) injection of DOX (15 mg/kg). DOX increased serum creatinine, urea, sodium, and potassium levels. It elevated MDA levels in the renal tissue but decreased the concentration of GSH and the activity of GST, CAT, and SOD. Meanwhile, it decreased the level of immunomodulatory anti-inflammatory mediators: IL-10 and TGF-β, as well as the activity of MPO but increased the level of IL-6, TNF-α, and caspase-3 in the renal tissue. DOX has upregulated COX-2, caspase-9, and Bax gene expression and downregulated the Bcl-2 gene expression. Immunolabeling of renal tubular epithelium in DOX-intoxicated rats was moderate to strong against Bax, COX-2, and NF-kβ and weak against Bcl-2. Treatment with CME significantly restored the levels of kidney function parameters and the levels of oxidative stress markers. It stimulated the production of IL-10 and TGF-β and decreased the level of IL-6 and TNF-α. CME reverted the gene expression of COX-2, caspase-9, and Bax. Microscopically, CME alleviated the DOX-induced renal damage. Phytochemical analysis revealed the presence of 26 compounds in the CME. No signs of acute toxicity were recorded by CME up to 4000 mg/kg b. wt. orally into mice. Finally, CME could effectively alleviate the deleterious effects of DOX on the kidney. The safety of carob extract encourages its use in the preparation of valuable therapeutic agents.

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Protection from doxorubicin-induced nephrotoxicity by clindamycin: novel antioxidant, anti-inflammatory and anti-apoptotic roles

Cited by 30 publications

References 46 publications

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Acylated ghrelin protects against doxorubicin‐induced nephropathy by activating silent information regulator 1

Ceratonia siliqua pods (Carob) methanol extract alleviates doxorubicin-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways in rats

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