Protective effect of Momordica charantia against Hepatorenal toxicity induced by Potassium bromate (KBrO3) in rats
Abstract
This study aims to evaluate the effects of Momordica charantia on hepatorenal toxicity caused by potassium bromate (KBrO3) in rats. Wistar rats were divided into 4 groups as control, KBrO3, bitter melon (MC), and KBrO3+MC. Examining the antioxidant enzyme grade of the kidney tissues, it was found that the enzyme activities of catalase (CAT) (P<0.05), glutathione peroxidase (GSH–Px) (P<0.01), and superoxide dismutase (SOD) (P<0.01) decreased in the KBrO3 group in comparison to the control. There was a significant decrease (P<0.001) in glutathione (GSH) levels and an increase (P<0.01) in malondialdehyde (MDA) level in the KBrO3 group in comparison to the control. Examining the antioxidant enzyme activities in liver tissue, it was determined that CAT, GSH–Px, and SOD enzymes reduced significantly (P<0.05, P<0.01, and P<0.001, respectively) in the KBrO3 group in comparison to the control, and the enzyme activity of decreased CAT, GSH–Px, and SOD enzymes significantly elevated (P<0.01) in the MC group. There was a reduction in GSH level in the KBrO3 group in comparison to the control (P<0.01), while an increase was recorded in the KBrO3+MC group (P<0.05). MDA level in liver tissue increased in KBrO3 group in comparison to the control (P<0.01) and MC decreased the MDA level. Histopathological analysis results indicate severe degenerative and necrotic lesions in hepatorenal histoarchitecture of KBrO3 rats in comparison to the control. However, application of MC+KBrO3 significantly reduced the induced hepatorenal injury with a concomitant increase in histopathological lesions. From the immunohistochemical aspect, MC revealed apoptosis concomitant with the suppression of necrosis in the KBrO3-treated rats as demonstrated by the caspase-3 activity.
Downloads
References
Bayomy NA, Soliman GM, Abdelaziz EZ. Effect of potassium bromate on the liver of adult male albino rat and a possible protective role of vitamin C: Histological, immunohistochemical, and biochemical study. Anat. Rec. [Internet]. 2016; 299(9):1256-1269. doi: https://doi.org/f82fbz DOI: https://doi.org/10.1002/ar.23386
Hassan I, Ebaid HM, Alhazza I, Al–Tamimi, J. The alleviative effect of vitamin B2 on potassium bromate–induced hepatotoxicity in male rats. Biomed. Res. Int. [Internet]. 2020; 30:8274261. doi: https://doi.org/pp6b DOI: https://doi.org/10.1155/2020/8274261
Wahba HMA, Ibrahim TAA. Protective effect of flaxseed oil and vitamin E on potassium bromate–induced oxidative stress in male rats. Int. J. Curr. Microbiol. App. Sci. [Internet]. 2013 [cited Feb. 22 2025]; 2(9):299-309. Available in: https://goo.su/2pxI1Ty
Ali BH, Za’abi MA, Karaca T, Suleimani YA, Balushi KAA, Manoj P, Ashique M, Nemmar A. Potassium bromate–induced kidney damage in rats and the effect of gum acacia thereon. Am. J. Transl. Res. [Internet]. 2018 [cited Jan. 15 2025]; 10(1):126-137. Available in: https://goo.su/n3zQ8v
Oyewo OO, Onyije FM, Awoniran PO. Hepatotoxic effect of potassium bromate on the liver of wistar rats. J. Morphol. Sci. [Internet]. 2013 [cited Jan. 15 2025]; 30(2)107-114. Available in: https://goo.su/Kjtofu
Ahmad MK, Khan AA, Ali SN, Mahmood R. Chemoprotective effect of taurine on potassium bromate–induced DNA damage, DNA–protein cross–linking and oxidative stress in rat intestine. Plos One. [Internet]. 2015; 10(3):e0119137. doi: https://doi.org/f69r7m DOI: https://doi.org/10.1371/journal.pone.0119137
Ajarem J, Altoom NG, Allam AA, Maodaa SN, Abdel– Maksoud MA, Chow BK. Oral administration of potassium bromate induces neurobehavioral changes, alters cerebral neurotransmitters level and impairs brain tissue of swiss mice. Behav. Brain Funct. [Internet]. 2016; 12(1):14. doi: https://doi.org/pp6c DOI: https://doi.org/10.1186/s12993-016-0098-8
Ahmad MK, Zubair H, Mahmood R. DNA damage and DNA– protein cross–linking induced in rat intestine by the water disinfection by–product potassium bromate. Chemosphere [Internet]. 2013; 91(8):1221-1224. doi: https://doi.org/f4svz3 DOI: https://doi.org/10.1016/j.chemosphere.2013.01.008
Ahmad MK, Khan AA, Mahmood R. Taurine ameliorates potassium bromate–induced kidney damage in rats. Amino Acids [Internet]. 2013; 45:1109-1121. doi: https://doi.org/f5c9ck DOI: https://doi.org/10.1007/s00726-013-1563-4
Malekshahi H, Bahrami G, Miraghaee S, Ahmadi SA, Sajadimajd S, Hatami R, Mohammadi B, Keshavarzi S. Momordica charantia reverses type II diabetes in rat. J. Food Biochem. [Internet]. 2019; 43(11):e13021. doi: https://doi.org/gjtcgn DOI: https://doi.org/10.1111/jfbc.13021
Blum A, Loerz C, Martin HJ, Staab–Weijnitz C. A, Maser E. Momordica charantia extract, a herbal remedy for type 2 diabetes, contains a specific 11β–hydroxysteroid dehydrogenase type 1 inhibitor. J. Steroid Biochem. Mol. Biol. [Internet]. 2012; 128(1-2):51-55. doi: https://doi.org/dkvffx DOI: https://doi.org/10.1016/j.jsbmb.2011.09.003
Ghous T, Aziz N, Mehmood Z, Andleeb S. Comparative study of antioxidant, metal chelating and antiglycation activities of Momordica charantia flesh and pulp fractions. Pak. J. Pharm. Sci. [Internet]. 2015 [cited Jan. 12 2025]; 28(4):1217-1223. Available in: https://goo.su/5Eemw
Abas R, Othman F, Thent ZC. Protective effect of Momordica charantia fruit extract on hyperglycaemia–induced cardiac fibrosis. Oxid. Med. Cell. Longev. [Internet]. 2014; 2014:429060. doi: https://doi.org/gb63fm DOI: https://doi.org/10.1155/2014/429060
Duan ZZ, Zhou XL, Li YH, Zhang F, Li FY, Su–Hua Q. Protection of Momordica charantia polysaccharide against intracerebral hemorrhage–induced brain injury through JNK3 signaling pathway. J. Recept. Signal Transduct. Res. [Internet]. 2015; 35(6):523-529. doi: https://doi.org/pp6d DOI: https://doi.org/10.3109/10799893.2014.963871
Deng Y, Tang Q, Zhang Y, Zhang R, Wei Z, Tang X, Zhang M. Protective effect of Momordica charantia water extract against liver injury in restraint–stressed mice and the underlying mechanism. Food Nutr. Res. [Internet]. 2017; 61(1):1348864. doi: https://doi.org/pp6f DOI: https://doi.org/10.1080/16546628.2017.1348864
Singh J, Adeghate E, Cummings E, Sharma AK, Singh J. Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin–induced diabetes mellitus in rat. Mol. Cell. Biochem. [Internet]. 2004; 261:63-70. doi: https://doi.org/ffddq2 DOI: https://doi.org/10.1023/B:MCBI.0000028738.95518.90
Sitasawad SL, Shewade Y, Bhonde R. Role of bitter gourd fruit juice in STZ–induced diabetic state in vivo and in vitro. J. Ethnopharmacol. [Internet]. 2000; 73(1-2):71-79. doi: https://doi.org/fprgmn DOI: https://doi.org/10.1016/S0378-8741(00)00282-8
Xia E, Rao G, Remmen VH, Heydari AR, Richardson A. Activites of antioxidant enzymes in various tissues of male fischer 344 rats are altered by food restriction. J. Nutr. [Internet]. 1995; 125(2):195-201. doi: https://doi.org/pp6g DOI: https://doi.org/10.1093/jn/125.2.195
Rizzi R, Caroli A, Bolla P, Acciaioli A, Pagnacco G. Variability of reduced glutathione levels in Massese ewes and its effect on daily milk production. J. Dairy Res. [Internet]. 1988; 55(3):345-353. doi: https://doi.org/bmpd36 DOI: https://doi.org/10.1017/S0022029900028600
Jain SK, McVie R, Duett J, Herbst JJ. Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes [Internet]. 1989; 38(12):1539-1543. doi: https://doi.org/pp6h DOI: https://doi.org/10.2337/diabetes.38.12.1539
Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. [Internet]. 1967; 70(1):158-169. PMID: 6066618. Available in: https://goo.su/CMTkD
Sun YI, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin. Chem. [Internet]. 1988; 34(3):497-500. doi: https://doi.org/gj74fn DOI: https://doi.org/10.1093/clinchem/34.3.497
Aebi H. Catalase in vitro. Methods Enzymol. [Internet]. 1984; 105:121-126. doi: https://doi.org/dnf7v9 DOI: https://doi.org/10.1016/S0076-6879(84)05016-3
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin Phenol Reagent. J. Biol. Chem. [Internet]. 1951; 193(1):265-275. doi: https://doi.org/ghv6nr DOI: https://doi.org/10.1016/S0021-9258(19)52451-6
Dommels YE, Butts CA, Zhu S, Davy M, Martell S, Hedderley D, Barnett MPG, McNabb WC, Roy NC. Characterization of intestinal inflammation and identification of related gene expression changes in mdr1a–/ – mice. Genes Nutr. [Internet]. 2007; 2(2):209-223. doi: https://doi.org/bq6m76 DOI: https://doi.org/10.1007/s12263-007-0051-4
Krause WJ. The art of examining and interpreting histological preparations: A student handbook. Pearl River (NY, USA): The Pathernon Publishing Group. 2001. 176 p.
Baratta JL, Ngo A, Lopez B, Kasabwalla N, Longmuir KJ, Robertson RT. Cellular organization of normal mouse liver: a histological, quantitative immunocytochemical, and fine structural analysis. Histochem. Cell. Biol. [Internet]. 2009; 131:(6):713-726. doi: https://doi.org/b72mpt DOI: https://doi.org/10.1007/s00418-009-0577-1
Shanmugavel V, Santhi KK, Kurup AH, Kalakandan S, Anandharaj A, Rawson A. Potassium bromate: effects on bread components, health, environment and method of analysis: a review. Food Chem. [Internet]. 2020; 311:125964. doi: https://doi.org/pp6j DOI: https://doi.org/10.1016/j.foodchem.2019.125964
Ebaid H, Bashandy SAE, Abdel–Mageed AM, Al–Tamimi J, Hassan I, Alhazza IM. Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress. Nutr. Metab. [Internet]. 2020; 17(1):6. doi: https://doi.org/gmdwcr DOI: https://doi.org/10.1186/s12986-019-0419-7
Hong YA, Park CW. Catalytic antioxidants in the kidney. Antioxidants [Internet]. 2021; 10(1):130. doi: https://doi. org/pp6k DOI: https://doi.org/10.3390/antiox10010130
Florens N, Calzada C, Lyasko E, Juillard L, Soulage CO. Modified lipids and lipoproteins in chronic kidney disease: a new class of uremic toxins. Toxins [Internet]. 2016; 8(12):376. doi: https://doi.org/gmw4d5 DOI: https://doi.org/10.3390/toxins8120376
Ebhohimen IE, Ebhomielen JO, Edemhanria L, Osagie AO, Omoruyi JI. Effect of ethanol extract of aframomum angustifolium seeds on potassium bromate induced liver and kidney damage in Wistar rats. G. J. Pure Appl. Sci. [Internet]. 2020; 26(1):1-8. doi: https://doi.org/pp6m DOI: https://doi.org/10.4314/gjpas.v26i1.1
Alhazza IM, Hassan I, Ebaid H, Al–Tamimi J, Alwasel SH. Chemopreventive effect of riboflavin on the potassium bromate–induced renal toxicity in vivo. Naunyn Schmiedebergs Arch. Pharmacol. [Internet]. 2020; 393:2355-2364. doi: https://doi.org/pp6n DOI: https://doi.org/10.1007/s00210-020-01938-7
Abdillah S, Inayah B, Kartiningsih Febrianti AB, Nafisa S. Acute and subchronic toxicity of Momordica Charantia L. fruits ethanolic extract in liver and kidney. Sys. Rev. Pharm. [Internet]. 2020 [cited Jan. 12 2025]; 11(12):2249-2255. Available in: https://goo.su/ZW8NJ
Zhang J, He L, Wang A, Wu B, Zhang P, Zhu Y, Jiang Y, Bai J, Xiao X. Responses of bitter melon saponins to oxidative stress and aging via the IIS pathway linked with sir-2.1 and hlh-30. J. Food Biochem. [Internet]. 2022; 46(12):e14456. doi: https://doi.org/pp6p DOI: https://doi.org/10.1111/jfbc.14456
Arun S, Kamollerd T, Tangsrisakda N, Bunsueb S, Chaiyamoon A, Wu ATH, Iamsaard S. Momordica charantia fruit extract with antioxidant capacity improves the expression of tyrosine– phosphorylated proteins in epididymal fluid of chronic stress rats. J. Integr. Med. [Internet]. 2022; 20(6):534-542. doi: https://doi.org/pp6q DOI: https://doi.org/10.1016/j.joim.2022.09.002
Krawczyk M, Burzynska–Pedziwiatr I, Wozniak LA, Bukowiecka– Matusiak M. Evidence from a systematic review and meta– analysis pointing to the antidiabetic effect of polyphenol–rich plant extracts from Gymnema montanum, Momordica charantia and Moringa oleifera. Curr. Issues Mol. Biol. [Internet]. 2022; 44(2):699-717. doi: https://doi.org/pp6r DOI: https://doi.org/10.3390/cimb44020049
Farah N, Bukhari SA, Ali M, Naqvi SAR, Mahmood S. Phenolic acid profiling and antiglycation studies of leaf and fruit extracts of tyrosine primed Momordica charantia seeds for possible treatment of diabetes mellitus. Pak. J. Pharm. Sci. [Internet]. 2018; 31(6):2667-2672. PMID: 30587477. Available in: https://goo.su/tbqNv
Mahmoud MF, El Ashry FE, El Maraghy NN, Fahmy A. Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin–induced diabetic rats. Pharm. Biol. [Internet]. 2017; 55(1):758-765. doi: https://doi.org/gjtcfk DOI: https://doi.org/10.1080/13880209.2016.1275026
Wang Q, Wu X, Shi F, Liu Y. Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ–induced type 2 diabetic mice. Biomed. Pharmacother. [Internet]. 2019; 109:744-750. doi: https://doi.org/gjtcfd DOI: https://doi.org/10.1016/j.biopha.2018.09.098
Zhang C, Huang M, Hong R, Chen H. Preparation of a Momordica charantia L. polysaccharide–chromium (III) complex and its anti–hyperglycemic activity in mice with streptozotocin–induced diabetes. Int. J. Biol. Macromol. [Internet]. 2019; 122:619-627. doi: https://doi.org/gjtcgf DOI: https://doi.org/10.1016/j.ijbiomac.2018.10.200
Raish M, Ahmad A, Jan BL, Alkharfy KM, Ansari MA, Mohsin K, Jenoobi FA, Al–Mohizea A. Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats. Int. J. Biol. Macromol. [Internet]. 2016; 91:394-399. doi: https://doi.org/f83pgc DOI: https://doi.org/10.1016/j.ijbiomac.2016.05.090
Wen JJ, Gao H, Hu JL, Nie QX, Chen HH, Xiong T, Nie SP, Xie MY. Polysaccharides from fermented Momordica charantia ameliorate obesity in highfat induced obese rats. Food Funct. [Internet]. 2019; 10(1):448-457. doi: https://doi.org/pp6s DOI: https://doi.org/10.1039/C8FO01609G
Zhang F, Lin L, Xie J. A mini–review of chemical and biological properties of polysaccharides from Momordica charantia. Int. J. Biol. Macromol. [Internet]. 2016; 92:246-253. doi: https://doi.org/f88wnk DOI: https://doi.org/10.1016/j.ijbiomac.2016.06.101
Chen F, Huang G, Huang H. Preparation, analysis, antioxidant activities in vivo of phosphorylated polysaccharide from Momordica charantia. Carbohydr. Polym. [Internet]. 2021; 252:117179. doi: https://doi.org/pp6t DOI: https://doi.org/10.1016/j.carbpol.2020.117179
Ben Saad H, Driss D, Ellouz Chaabouni S, Boudawara T, Zeghal KM, Hakim A, Ben Amara I. Vanillin mitigates potassium bromate induced molecular, biochemical and histopathological changes in the kidney of adult mice. Chem. Biol. Interact. [Internet]. 2016; 252:102-113. doi: https://doi.org/f8j52z DOI: https://doi.org/10.1016/j.cbi.2016.04.015
Gheth EMM, Eldurssi IS, Algassi AAH, Abdalla GMA, Hamad MAS. Histopathological effects of potassium bromate on liver male rat’s and possible protective role of Ruta chalepensis L. (Rutacae) oil extract. Asian J. Pharm. Res. [Internet]. 2019; 7(2):93-97. doi: https://doi.org/pp6v DOI: https://doi.org/10.22270/ajprd.v7i2.473
Abdel–Latif AS, Abu–Risha SE, Bakr SM, El–Kholy WM, El–Sawi MR. Potassium bromate–induced nephrotoxicity and potential curative role of metformin loaded on gold nanoparticles. Sci. Prog. [Internet]. 2021; 104(3):1-29. doi: https://doi.org/gmdvgg DOI: https://doi.org/10.1177/00368504211033703