ORIGINAL_ARTICLE The research study determined the effect of bovine whey supplementation in rats fed on high-fat diet on occurrence of myocardium damage and disfunction in its offspring. Eighty virgin female rats (Rattus norvegicus) (100-110 g body weight) were used for this study. Following mating, the pregnant rats were categorized into four groups: control, whey supplemented (W), high-fat diet (FD) and high-fat diet and whey supplemented group (FD+W). Whey supplementation alone or in combination with a high-fat diet was administered every other day during the gestation and lactation period. Offspring rats at the age of 1, 7, 14 and 21-day post-partum were sacrificed and their hearts were processed for histological, p53 immunohistochemistry, transmission electron microscopy and biochemical markers for cell damage. Offspring from the FD+W group exhibited improvement of the myocardium histological picture. Moreover, there was a lower accumulation of lipid deposits and regular organization of cardiomyocyte bands and intercalated discs. A lower p53 immune reaction and lower single strand DNA damage was noticed. The levels of the antioxidant enzymes (SOD and catalase) in the myocardium were increased, whereas the contents of IL6, MDA and caspase-3 were decreased, resulting in a reduction in inflammation and cell death. In conclusion, supplementation of whey to mother rats fed with high-fat diet alleviated the markers of cardiomyocyte injury in its offspring due to its antioxidant effect. https://macvetrev.mk/Files/Article/2022/10.2478/macvetrev-2022-0017/macvetrev-2022-0017.pdf 2022-03-15T09:00:00 89 99 10.2478/macvetrev-2022-0017 high-fat diet rats myocardium offspring whey Eman Mohammed Emara false 1 Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt AUTHOR Hassan Ibrahim El-Sayyad elsayyad@mans.edu.eg false 2 Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt LEAD_AUTHOR Heba Atef El-Ghaweet false 3 Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt AUTHOR Hoffman, D.J., Powell, T.L., Barrett, E.S., Hardy, D.B. (2021). Developmental origins of metabolic diseases. Physiol Rev. 101(3): 739-795. PMid:33270534 1 10.1152/physrev.00002.2020 Siddeek, B., Mauduit, C., Chehade, H., Blin, G., Liand, M., Chindamo, M. et al. (2019). Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis. Cell Death Discov. 5, 71. PMid:30854230 PMCid:PMC6397280 2 10.1038/s41420-019-0153-y Mdaki, K.S., Larsen, T.D., Wachal, A.L., Schimelpfenig, M.D., Weaver, L.J., Dooyema, S.D. et al. (2016). Maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancy through metabolic stress and mitochondrial dysfunction. Am J Physiol Heart Circ Physiol. 310, H681-H692. PMid:26801311 PMCid:PMC4867345 3 10.1152/ajpheart.00795.2015 Dunn, G.A., Bale, T.L. (2009). Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice. Endocrinology 150(11): 4999-5009. PMid:19819967 PMCid:PMC2775990 4 10.1210/en.2009-0500 Ferey, J.L.A., Boudoures, A.L., Reid, M., Drury, A., Scheaffer, S., Modi, Z. et al. (2019). A maternal high-fat, high-sucrose diet induces transgenerational cardiac mitochondrial dysfunction independently of maternal mitochondrial inheritance. Am J Physiol Heart Circ Physiol. 316(5): H1202-H1210. PMid:30901280 PMCid:PMC6580388 5 10.1152/ajpheart.00013.2019 Chatterton, D.E.W., Smithers, G., Roupas, P., Brodkorb, A. (2006). Bioactivity of β-lactoglobulin and α-lactalbumin-Technological implications for processing. Int Dairy J. 16(11): 1229-1240. 6 10.1016/j.idairyj.2006.06.001 Krissansen, G.W. (2007). Emerging health properties of whey proteins and their clinical implications. J Am Coll Nutr. 26(6): 713S-723S. PMid:18187438 7 10.1080/07315724.2007.10719652 El-Sayyad, H.I., El-Ghawet, H.A., El-Bayomi, K.S., Emara, E. (2020). Bovine whey improved the myocardial and lung damage of mother rats fed on a high fat diet. Stud Stem Cells Res Ther. 6(1): 001-008. 8 10.17352/sscrt.000014 Kandil, N.T.A.H. Sabry, D.A.M., Ashry, N.E.E., El-Sayyad, H.I.H. (2020). Therapeutic potential of whey against aging related cytological damage of adenohypophysis of rat. East African Scholars J Agri Life Sci. 3(9): 304-310. 9 10.36349/EASJALS.2020.v03i09.002 Sasaki, Y.F., Nishidate, E., Izumiyama, F., Matsusaka, N., Tsuda, S. (1997). Simple detection of chemical mutagens by the alkaline single-cell gel electrophoresis (Comet) assay in multiple mouse organs. Mutat Res. 391(3): 215-231. 10 10.1016/S1383-5718(97)00073-9 Deeg, R., Ziegenhorn, J. (1983). Kinetic enzymic method for automated determination of total cholesterol in serum. Clin Chem. 29(10): 1798-1802. PMid:6577981 11 10.1093/clinchem/29.10.1798 Fossati, P., Prencipe, L. (1982). Serum triglycerides determined colorimetrically with an enzyme that proceduces hydrogen peroxide. Clin Chem. 28(10): 2077-2080. PMid:6812986 12 10.1093/clinchem/28.10.2077 Grove, T.H. (1979). Effect of reagent PH on determination of the high-density lipoprotein cholesterol by precipitation with sodium phototungestate-magnesium. Clin Chem. 25(4): 560-564. PMid:38018 13 10.1093/clinchem/25.4.560 Friedewald, W.T., Levy, R.I., Fredrickson, D.S. (1972). Estimation of low density lipoprotein cholesterol in plasma without use preparative ultracentri-fuge. Clin Chem. 18(6): 499-502. PMid:4337382 14 10.1093/clinchem/18.6.499 Niskikimi, M., Rao, N., Yaki, K. (1972). The occurrence of superoxide anion in the reaction of reduced phenazinemethosulfate and molecular oxygen. Biochem Biophys Res Commun. 46(2): 849-854. 15 10.1016/S0006-291X(72)80218-3 Bock, P.P., Kramer, R., Pavelka, M. (1980). Peroxisomes and related particles. In M. Alfert, W. Beermann, L. Goldstein, K.R. Porter, P. Sitte (Eds.), Cell Biology Monographs 7 (pp. 44-74). Springer, Berlin 16 10.1007/978-3-7091-2055-2_2 Ohkawa, H., Ohishi, N., Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 95(2): 351-358. 17 10.1016/0003-2697(79)90738-3 Ribaroff, G.A., Wastnedge, E., Drake, A.J., Sharpe, R.M., Chambers, T.J.G. (2017). Animal models of maternal high fat diet exposure and effects on metabolism in offspring: a meta-regression analysis. Obes Rev. 18(6): 673-686. PMid:28371083 PMCid:PMC5434919 18 10.1111/obr.12524 Butruille, L., Marousez, L., Pourpe, C., Oger, F., Lecoutre, S., Catheline, D. et al. (2019). Maternal high-fat diet during suckling programs visceral adiposity and epigenetic regulation of adipose tissue stearoyl-CoA desaturase-1 in offspring. Int J Obes (Lond). 43(12): 2381-2393. PMid:30622312 19 10.1038/s41366-018-0310-z Guzzardi, M.A., Liistro, T., Gargani, L., Ait Ali, L., D’Angelo, G., Rocchiccioli, S. et al. (2018). Maternal obesity and cardiac development in the offspring: Study in human neonates and minipigs. JACC Cardiovasc Imaging. 11(12): 1750-1755. PMid:29153568 20 10.1016/j.jcmg.2017.08.024 Giacco, F., Brownlee, M. (2010). Oxidative stress and diabetic complications. Circ Res. 107(9): 1058-1070. PMid:21030723 PMCid:PMC2996922 21 10.1161/CIRCRESAHA.110.223545 Magalhães, D.A., Kume, W.T., Correia, F.S., Queiroz, T.S., Allebrandt Neto, E.W., Santos, M.P.D. et al. (2019). High-fat diet and streptozotocin in the induction of type 2 diabetes mellitus: a new proposal. An Acad Bras Cienc. 91(1): e20180314. PMid:30916157 22 10.1590/0001-3765201920180314 Xiang, L., Zhang, Q., Chi, C., Wu, G., Lin, Z., Li, J. et al. (2020). Curcumin analog A13 alleviates oxidative stress by activating Nrf2/ARE pathway and ameliorates fibrosis in the myocardium of highfat- diet and streptozotocin-induced diabetic rats. Diabetol Metab Syndr. 12, 1. PMid:31921358 PMCid:PMC6947902 23 10.1186/s13098-019-0485-z Attia, H.M., Taha, M. (2018). Protective effect of captopril on cardiac fibrosis in diabetic albino rats: a histological and immunohistochemical study. Benha Med J. 35(3): 378-385. 24 10.4103/bmfj.bmfj_122_18 Sheen, J.M., Yu, H.R., Tain, Y.L., Tsai, W.L., Tiao, M.M., Lin, I.C., Tsai, C.C., Lin, Y.L., Huang, L.T. (2018). Combined maternal and postnatal high-fat diet leads to metabolic syndrome and is effectively reversed by resveratrol: a multiple-organ study. Sci Rep. 8(1): 5607. PMCid:PMC5884801 25 10.1038/s41598-018-24010-0PMid:29618822 Dasgupta, A., Chow, L., Wells, A., Datta, P. (2001). Effect of elevated concentration of alkaline phosphatase on cardiac troponin I assays. J Clin Lab Anal. 15(4): 175-177. PMid:11436198 PMCid:PMC6807912 26 10.1002/jcla.1023 You, A.H., Han, D.W., Ham, S.Y., Lim, W., Song, Y. (2019). Serum alkaline phosphatase as predictor of cardiac and cerebrovascular complications after lumbar spinal fusion surgery in elderly: A retrospective study. J Clin Med. 8(8): 1111. PMid:31357535 PMCid:PMC6723677 27 10.3390/jcm8081111 Al-Gebaly, A.S. (2019). Ameliorating role of whey syrup against ageing- related damage of myocardial muscle of Wistar Albino rats. Saudi J Biol Sci. 26(5): 950-956. PMid:31303824 PMCid:PMC6600591 28 10.1016/j.sjbs.2018.03.014 Martin, M., Kopaliani, I., Jannasch, A., Mund, C., Todorov, V., Henle, T. et al. (2015). Antihypertensive and cardioprotective effects of the dipeptide isoleucine-tryptophan and whey protein hydrolysate. Acta Physiol (Oxf). 215(4): 167-176. PMid:26297928 29 10.1111/apha.12578 El-Shinnawy, N.A., Abd Elhalem, S.S., Haggag, N.Z., Badr, G. (2018). Ameliorative role of camel whey protein and rosuvastatin on induced dyslipidemia in mice. Food Funct. 9(2): 1038-1047. PMid:29349446 30 10.1039/C7FO01871A Bartfay, W.J., Davis, M.T., Medves, J.M., Lugowski, S. (2003). Milk whey protein decreases oxygen free radical production in a murine model of chronic iron-overload cardiomyopathy. Can J Cardiol. 19(10): 1163-1168. 31 Mann, P.E., Huynh, K., Widmer, G. (2018). Maternal high fat diet and its consequence on the gut microbiome: A rat model. Gut Microbes. 9(2): 143-154. PMid:29135334 PMCid:PMC5989793 32 10.1080/19490976.2017.1395122 Pace, R.M., Prince, A.L., Ma, J., Belfort, B.D.W., Harvey, A.S., Hu, M. et al. (2018). Modulations in the offspring gut microbiome are refractory to postnatal synbiotic supplementation among juvenile primates. BMC Microbiol. 18, 28. PMid:29621980 PMCid:PMC5887201 33 10.1186/s12866-018-1169-9