A role of connexin 43 on the drug-induced liver, kidney, and gastrointestinal tract toxicity with associated signaling pathways

Katturajan, Ramkumar; Sabina, Evan Prince

doi:10.1016/j.lfs.2021.119629

Cited by 17 publications

(15 citation statements)

References 150 publications

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“…Arsenic, a trivalent inorganic arsenic, also is a worldwide environmental pollutant and a human carcinogen ( 6 , 37 , 38 ). As MgIG has good lipophilicity, it easily penetrates the cell membrane to bind to the receptor protein and the target cell receptor of steroid hormones, thereby exerting hormonal effects (such as remission lipid metabolism disorder) ( 24 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

“…The kidney is an important organ that not only can maintain blood pressure and eliminate waste, but also can maintain and regulate body fluid, such as acid-base balance ( 5 ). Kidney damage or nephrotoxicity leads to the impairment of detoxification and excretion functions, which can be confirmed by renal markers such as blood urea nitrogen (BUN), creatinine (CRE) and CRE clearance ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

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Nephroprotective effect of magnesium isoglycyrrhizinate against arsenic trioxide‑induced acute kidney damage in mice

Wei

Sun

et al. 2022

Exp Ther Med

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Magnesium isoglycyrrhizinate (MgIG) has antiinflammatory, antioxidative, antiviral and anti-hepatotoxic effects. However, protective effects of MgIG against renal damage caused by arsenic trioxide (ATO) have not been reported. The present study aimed to clarify the protective function of MgIG on kidney damaged induced by ATO. Other than the control group and the group treated with MgIG alone, mice were injected intraperitoneally with ATO (5 mg/kg/day) for 7 days to establish a mouse model of kidney damage. On the 8th day, blood and kidney tissue were collected and the inflammatory factors and antioxidants levels in the kidney tissue and serum were measured. The expression of protein levels of caspase-3, Bcl-2, Bax, Toll-like receptor-4 (TLR4) and nuclear factor-κB (NF-κB) were determined via western blot analysis. In the renal tissue of mice, ATO exposure dramatically elevated markers of oxidative stress, apoptosis and inflammation. However, MgIG could also restore the activities of urea nitrogen and creatinine to normal levels, decrease the malondialdehyde level and reactive oxygen species formation and increase superoxide dismutase, catalase and glutathione activities. MgIG also ameliorated the morphological abnormalities generated by ATO, reduced inflammation and apoptosis and inhibited the TLR4/NF-κB signaling pathway. In conclusion, MgIG may mitigate ATO-induced kidney damage by decreasing apoptosis, oxidative stress and inflammation and its mechanism may be connected to the inhibition of TLR4/NF-κB signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nephroprotective effect of magnesium isoglycyrrhizinate against arsenic trioxide‑induced acute kidney damage in mice

Wei

Sun

et al. 2022

Exp Ther Med

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“…48 This is being explored as a possible new therapeutic field with new drugs against Cx43 as a target, which are already being studied in clinical trials. 46…”

Section: Discussionmentioning

confidence: 99%

“…8 Several of these events (such as cell death or metabolism of toxics) are controlled by hemichannels and most specifically by Cx43. 46 For instance, Cx hemichannels opening increases under oxidative stress conditions 47 but anomalous opening of Cx43 hemichannels can cause endothelial cell dysfunction. 34 In addition, Cx43 has the potential to initiate the immune system to cause cell death.…”

Section: Discussionmentioning

confidence: 99%

Connexin 43 Expression in Cutaneous Biopsies of Lupus Erythematosus

Fernández-Flores

Varela-Vázquez

Mayán

et al. 2022

The American Journal of Dermatopathology

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Introduction:Gap junctions are channels between adjacent cells formed by connexins (Cxs). Cxs also form hemichannels that connect the cell with its extracellular milieu. These channels allow the transport of ions, metabolites, and small molecules; therefore, Cxs, and more specifically, connexin (Cx) 43 has been demonstrated to be in control of several crucial events such as inflammation and cell death.Material and methods:We examined the immunostaining of Cx43 in the endothelia of the cutaneous blood vessels of biopsies from 28 patients with several variants of lupus erythematosus.Results:In 19 cases (67.86%), staining of more than half of the dermal vessels including both vessels of the papillary and of the reticular dermis was identified. Only in 4 cases (14.28%), less than 25% of the vessels in the biopsy showed expression of the marker.Conclusions:Our results suggest a role of Cx43 in regulating the endothelial activity in lupus erythematosus, which also opens a door for targeted therapeutic options.

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“…GJA1 (encoding Cx43 ) is a member of the connexin family that possesses both tumor-suppressive, and oncogenic functions ( Aasen et al, 2019 ). The misregulation of connexins affects a process of cell differentiation, inflammation, and cell death ( Katturajan and Evan Prince, 2021 ). GJA1 is a highly attractive target for delivering drugs directly into the cytoplasm of cancer cells, due to the permeability of gap junction channels to small molecules and macromolecules ( Bonacquisti and Nguyen, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Therapeutic Genes for More Precise Treatment of Esophageal Squamous Cell Carcinoma and Adenocarcinoma

Polewko-Klim

Zhu

et al. 2022

Front. Genet.

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The standard therapy administered to patients with advanced esophageal cancer remains uniform, despite its two main histological subtypes, namely esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (AC), are being increasingly considered to be different. The identification of potential drug target genes between SCC and AC is crucial for more effective treatment of these diseases, given the high toxicity of chemotherapy and resistance to administered medications. Herein we attempted to identify and rank differentially expressed genes (DEGs) in SCC vs. AC using ensemble feature selection methods. RNA-seq data from The Cancer Genome Atlas and the Fudan-Taizhou Institute of Health Sciences (China). Six feature filters algorithms were used to identify DEGs. We built robust predictive models for histological subtypes with the random forest (RF) classification algorithm. Pathway analysis also be performed to investigate the functional role of genes. 294 informative DEGs (87 of them are newly discovered) have been identified. The areas under receiver operator curve (AUC) were higher than 99.5% for all feature selection (FS) methods. Nine genes (i.e., ERBB3, ATP7B, ABCC3, GALNT14, CLDN18, GUCY2C, FGFR4, KCNQ5, and CACNA1B) may play a key role in the development of more directed anticancer therapy for SCC and AC patients. The first four of them are drug targets for chemotherapy and immunotherapy of esophageal cancer and involved in pharmacokinetics and pharmacodynamics pathways. Research identified novel DEGs in SCC and AC, and detected four potential drug targeted genes (ERBB3, ATP7B, ABCC3, and GALNT14) and five drug-related genes.

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A role of connexin 43 on the drug-induced liver, kidney, and gastrointestinal tract toxicity with associated signaling pathways

Cited by 17 publications

References 150 publications

Nephroprotective effect of magnesium isoglycyrrhizinate against arsenic trioxide‑induced acute kidney damage in mice

Nephroprotective effect of magnesium isoglycyrrhizinate against arsenic trioxide‑induced acute kidney damage in mice

Connexin 43 Expression in Cutaneous Biopsies of Lupus Erythematosus

Identification of Candidate Therapeutic Genes for More Precise Treatment of Esophageal Squamous Cell Carcinoma and Adenocarcinoma

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