The Role of Connexin in Cutaneous Adverse Drug Reactions (CADRs) in Patients with Increasing Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)
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Background: The occurrence of Cutaneous Adverse Drug Reactions (CADRs) is relatively rare but can be fatal when causing organ failure, especially in the liver. The supporting examinations to determine liver injury are aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Connexin-32 (Cx32) and connexin-43 (Cx43) are gap junction proteins that can be found in the liver and allegedly have a role in the mechanism of liver injury. To date, correlations between the level of connexin and aminotransferases enzyme in humans with CADRs cases are still unclear. Purpose: To determine the correlations between Cx32/Cx43 and AST/ALT levels in CADRs cases. Methods: This was a retrospective study, data collected from inpatient and outpatient's medical records, Department of Dermatology and Venereology of Dr. Sardjito Hospital, from 2011–2015. Result: A total of 25 patients with CADRs and 35 healthy controls were included in this study. The levels between Cx32 and AST, Cx32 and ALT, Cx43 and AST, and Cx43 and ALT were not significantly correlated in CADRs cases (p>0.05). Both Cx32 and Cx43 were not significantly different between patients with and without CADRs (p>0.05). Confounding factors such as gender were not associated with this study (p>0.05). Conclusion: There was no correlation between levels of Cx32/Cx43 and increasing AST/ALT in CADRs cases. Therefore, further study is necessary to conclude the correlation between connexin and aminotransferase enzyme in CADRs patients.
Khalil H, Huang C. Adverse drug reactions in primary care: a scoping review. BMC Health Serv Res 2020; 20:5.
Oshikoya KA, Ogunyinka IA, Ogar CK, Abiola A, Ibrahim A, Oreagba IA. Severe cutaneous adverse drug reactions manifesting as Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the national pharmacovigilance center in Nigeria: a database review from 2004 to 2017. Ther Adv Drug Saf 2020; 11: 1-18.
Hina A, Masood S, Jamil S, Tabassum S, Jalil P, Ghulam U. Prevalence of clinical spectrum of cutaneous adverse drug reactions in patients presenting at a tertiary care hospital in Pakistan. Cureus 2021; 13(4):e14568.
Baldo B, Pham N. Drug Allergy: Clinical aspects, diagnosis, mechanisms, structure-Activity Relationships. New York: Springer; 2013.
Böhm R, Proksch E, Schwarz T, Cascorbi I. Drug hypersensitivity. Dtsch í„rztebl Int 2018; 115(29–30): 501–12.
Lee T, Lee YS, Yoon S-Y, Kim S, Bae Y-J, Kwon H-S, et al. Characteristics of liver injury in drug-induced systemic hypersensitivity reaction. J Am Acad Dermatol 2013; 69(3): 407–15.
Yanguas SC, Willebrords J, Maes M, da Silva TC, Pereira IVA, Cogliati B, et al. Connexins and pannexins in liver damage. EXCLI J 2016; 15: 177–86.
Nakashima Y, Ono T, Yamanoi A, El-Assal ON, Kohno H, Nagasue N. Expression of gap junction protein connexin32 in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. J Gastroenterol 2004; 39(8): 763–8.
Yamaoka K, Nouchi T, Kohashi T, Marumo F, Sato C. Expression of gap junction protein connexin 32 in chronic liver diseases. Liver 2000; 20(2): 104–7.
Eugenín EA, González HE, Sánchez HA, Brañes MC, Sáez JC. Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro. Cell Immunol 2007; 247(2): 103–10.
Ogawa K, Pitchakarn P, Suzuki S, Chewonarin T, Tang M, Takahashi S, et al. Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells. Cancer Sci 2012; 103(5): 860–7.
Xiang Y, Wang Q, Guo Y, Ge H, Fu Y, Wang X, et al. Cx32 exerts anti-apoptotic and pro-tumor effects via the epidermal growth factor receptor pathway in hepatocellular carcinoma. J Exp Clin Cancer Res 2019; 38(1): 145.
Igarashi I, Makino T, Suzuki Y, Kai K, Teranishi M, Takasaki W, et al. Background lesions during a 24-month observation period in connexin 32-deficient mice. J Vet Med Sci 2013; 75(2): 207–10.
Naiki-Ito A, Asamoto M, Naiki T, Ogawa K, Takahashi S, Sato S, et al. Gap junction dysfunction reduces acetaminophen hepatotoxicity with impact on apoptotic signaling and connexin 43 protein induction in rat. Toxicol Pathol 2010; 38(2): 280–6.
Patel TK, Thakkar SH, Sharma D. Cutaneous adverse drug reactions in Indian population: A systematic review. Indian Dermatol Online J 2014; 5(Suppl 2): S76-86.
Tang N, Cai Z, Chen H, Cao L, Chen B, Lin B. Involvement of gap junctions in propylthiouracil"‘induced cytotoxicity in BRL"‘3A cells. Exp Ther Med 2019; 17(4): 2799–806.
Igarashi I, Maejima T, Kai K, Arakawa S, Teranishi M, Sanbuissho A. Role of connexin 32 in acetaminophen toxicity in a knockout mice model. Exp Toxicol Pathol 2014; 66(2–3): 103–10.
Maes M, McGill MR, da Silva TC, Abels C, Lebofsky M, de Araújo CMM, et al. Involvement of connexin43 in acetaminophen-induced liver injury. Biochim Biophys Acta 2016; 1862(6): 1111–21.
Boengler K, Rohrbach S, Weissmann N, Schulz R. Importance of Cx43 for right ventricular function. Int J Mol Sci 2021; 22(3): 987
Johnson RD, Camelliti P. Role of non-myocyte gap junctions and connexin hemichannels in cardiovascular health and disease: Novel Therapeutic Targets? Int J Mol Sci 2018; 19(3): 866.
Patel SJ, Milwid JM, King KR, Bohr S, Iracheta A, Li M, et al. Gap junction inhibition prevents drug-induced liver toxicity and fulminant hepatic failure. Nat Biotechnol 2012; 30(2): 179–83.
Wu X, Huang W, Luo G, Alain LA. Hypoxia induces connexin 43 dysregulation by modulating matrix metalloproteinases via MAPK signaling. Mol Cell Biochem 2013; 384(1–2): 155–62.
Chen CC, Kuo CY, Chen RF. Role of CAPE on cardiomyocyte protection via connexin 43 regulation under hypoxia. Int J Med Sci 2016; 13(10): 754–8.
Sato M, Jiao Q, Honda T, Kurotani R, Toyota E, Okumura S, et al. Activator of G protein signaling 8 (AGS8) is required for hypoxia-induced apoptosis of cardiomyocytes: role of G betagamma and connexin 43 (CX43). J Biol Chem 2009; 284(45): 31431–40.
Danon A, Zeevi-Levin N, Pinkovich DY, Michaeli T, Berkovich A, Flugelman M, et al. Hypoxia causes connexin 43 internalization in neonatal rat ventricular myocytes. Gen Physiol Biophys 2010; 29(3):222–33.
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