Cucumeropsis mannii (African White Melon) Seed Oil Mitigates Dysregulation of Redox Homeostasis, Inflammatory Response, and Apoptosis in Testis of Bisphenol A Exposed Male Rats
Keywords:CMSO, BPA, Testicular toxicity, Redox Homeostasis, Inflammations, Apoptosis
Testicular toxicity is a prime threat to male reproductive health. Humans are constantly exposed to Bisphenol A (BPA) via oral route, thus inducing reproductive toxicity. Cucumeropsis mannii seed oil (CMSO) has nutraceuticals with antioxidant potential. This present study investigated the potential of CMSO to mitigate testicular oxidative damages induced by exposure to BPA. Thirty-six (36) male Wistar albino rats, 2-3 months old, were randomly assigned into six (6) study groups; 3 control groups (CG1, CG2, and CG3) and 3 test groups (TG1, TG2, and TG3), respectively. CG1 rats received 1 ml of olive oil. CG2 rats received 100 mg/kg body weight of BPA. CG3 rats received 7.5 ml/Kg body weight of CMSO. TG1 rats were co-administered 100 mg/kg body weight of BPA and 7.5 ml/kg bodyweight of CMSO. TG2 rats were co-administered with 100 mg/kg body weight of BPA and 5 ml/kg body weight of CMSO. TG3 rats were co-administered with 100 mg/kg body weight of BPA and 2.5 ml/kg body weight of CMSO. After the trial, the rats' testes were extracted and taken for biochemical analysis. The result showed that the exposure of rats to BPA significantly (p < 0.05) increased the levels of ROS and MDA but considerably decreased the levels of GSH, CAT, SOD, GPx, IL-1β, IL-6, TNF-α, NF-ĸB, and Caspase-3 activity in the testicular homogenate. However, co-administration of BPA with CMSO significantly (p < 0.05) reversed all the dysregulations. This study reported that CMSO is a potential nutraceutical for mitigation of BPA-induced testicular oxidative damages.
Aebi, H. (1984). Catalase in vitro. In: Packer L edition, Methods of Enzymology. Academic Press, New York, pp, 121–126.
Agu, P. C., Aja, P. M., Ekpono, Ugbala Ezebuilo, Ogwoni, H. A., Ezeh, E. M., Oscar-Amobi, P. C., Agbor Asuk Atamgba, Ani, O. G., Awoke, J. N., Nwite, F. E., Ukachi, O. U., Orji, O. U., Nweke, P. C., Ugbala, Ejike Ekpono, Ewa, G. O., Igwenyi, I. O., Egwu, C. O., Alum, E. U., Chukwu, D. C. and Famurewa, A. C. (2022). Cucumeropsis mannii seed oil (CMSO) attenuates alterations in testicular biochemistry and histology against Bisphenol A-induced toxicity in male Wister albino rats. Heliyon, 8: e09162
Aja, P. M., Izekwe, F. I., Famurewa, A. C., Ekpono, E. U., Nwite, F. E., Igwenyi, I. O., Awoke, J. N., Ani, O. G., Aloke, C., Obasi, N. A., Udeh, K. U. and Ale, B. A. (2020). Hesperidin protects against cadmium-induced pancreatitis by modulating insulin secretion, redox imbalance, and iNOS/NF-ĸB signaling in rats. Life Sciences, 259: 118268.
Alboghobeish, S., Mahdavinia, M., Zeidooni, L., Samimi, A., Oroojan, A. A., Alizadeh, S., Dehghani, M. A., Ahangarpour, A. and Khorsandi, L. (2019). Efficacy of naringin against reproductive toxicity and testicular damages induced by bisphenol A in rats. Iranian Journal of Basic Medical Science, 22: 315-323.
Anhwange, B. A., Ikyenge, B. A., Nyiatagher, D. T. and Ageh, J. T. (2010). Chemical analysis of Citrullus lanatus (Thunb.), Cucumeropsis mannii (Naud.), and Telfairia occidentalis (Hook F.) seeds oils. Journal of Applied Sciences Research, 6(3): 265–268.
Aydo˘gan, M., Korkmaz, A., Barlas, N. and Kolankaya, D. (2009). Pro-oxidant effect of vitamin C coadministration with bisphenol A, nonylphenol, and octylphenol on the reproductive tract of male rats. Drug Chemistry and Toxicology, 33: 193–203.
Bashir, N., Manoharan, V. and Miltonprabu, S. (2016). Grape seed proanthocyanidins protect against cadmium-induced oxidative pancreatitis in rats by attenuating oxidative stress, inflammation, and apoptosis via Nrf-2/HO-1 signaling. Journal of Nutritional Biochemistry, 32: 128–141.
Behmanesh, M. A., Najafzadehvarzi, H. and Poormoosavi, S. M. (2018). Protective effect of aloe vera extract against bisphenol A-induced testicular toxicity in Wistar rats. Cell Journal, 20(2): 278-283.
Benke, G. M., Cheever, K. L., Mirer, F. E., and Murphy, S. D. (1974). Comparative toxicity, anticholinesterase action, and metabolism of methyl parathion and parathion in sunfish and mice. Toxicology & Applied Pharmacology, 197: 2897–110.
Besong, S. A., Ezekwe, M. O., Fosung, C. N., and Senwo, Z. N. (2011). "Evaluation of nutrient composition of African melon oilseed (Cucumeropsis mannii Naudin) for human nutrition. International Journal of Nutrition and Metabolism, 3(8): 103–108.
Buchbauer, G. (2000). The detailed analysis of essential oils leads to acc n understanding of their properties. Perfumer and flavourist, 25: 64-67.
Campos, J. F., Espindola, P. P. dT., Torquato, H. F. V., Vital, W. D., Justo, G. Z., Silva, D. B., Carollo, C. A., de Picoli, Souza, K., Paredes-Gamero, E. J. and dos Santos, E. L. (2017). Leaf and Root Extracts from Campomanesia adamantium (Myrtaceae) Promote Apoptotic Death of Leukemic Cells via Activation of Intracellular Calcium and Caspase-3. Frontier in Pharmacology, 8: 466.
Chitra, K. C., Latchoumycandane, C. and Mathur, P. P. (2003). Induction of oxidative stress by bisphenol A in the epididymal sperm of rats. Toxicology, 185: 119–127.
Cimmino, I., Fiory, F., Perruolo, G., Miele, C., Beguinot, F., Formisano, P. and Oriente, F. (2020). Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease. International Journal of Molecular Sciences, 21: 1561.
Cui, J. D. (2014). Biotechnological production and applications of Cordyceps militaris, a valued traditional Chinese medicine. Critical Review in Biotechnology, 35: 475–484.
da Silva, L. M., Pezzini, B. C. Somensi, L. B., Mariano, L. N., Mariott, M. and Boeing, T. (2019). Hesperidin, a citrus flavanone glycoside, accelerates the gastric healing process of acetic acid-induced ulcers in rats. Chemistry and Biological Interactions, 308: 45–50.
EL makawy, A., Eissa, F. I. and EI-Bamby, M. (2018). Flaxseed oil as a protective agent against bisphenol-A deleterious effects in male mice. Bulletin of the National Research Centre, 42(1): 5-9.
Elhamalawy, O. S., Eissa, F. I., ELmakawy, A. and EI-Bamaby, M. M. (2018). Bisphenol-A Hepatotoxicity and the Protective Role of Sesame Oil in Male Mice. Jordan Journal of Biological Sciences. 11(4): 461-467.
Famurewa, A. C., Asogwa, N. T., Aja, P. M., Akunna, G. G., Awoke, J. N., Ekeleme-Egedigwe, C. A. Maduagwuna, E. K., Folawiyo, A. M., Besong, E. E., Ekpono, E. U. and Nwoha, P. A. (2019). Moringa oleifera seed oil modulates redox imbalance and iNOS/NF-ĸB/caspase-3 signaling pathway to exert antioxidant, anti-inflammatory, and antiapoptotic mechanisms against anticancer drugs 5-fluorouracil-induced nephrotoxicity in rats. South African Journal of Botany, 127: 96–103.
Flohe, L., and Otting, F. (1984). Superoxide dismutase assays. Methods in Enzymology, 105: 101-104.
Ho, Y. S., Magnenat, J. L., Gargano, M., and Cao, J. (1998). The nature of antioxidant defense mechanisms: a lesson from transgenic studies. Environmental Health Perspective, 106:1219-1225.
Hu, C. and Kitts, D. D. (2000). Studies on the antioxidant activity of Echinacea root extract. Journal of Agricultural and Food Chemistry, 48: 1466–1472.
Huang, Y. Q., Wong, C. K., and Zheng, J. S. (2012). Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts. Environment International, 42: 91–99
Jacks, T. J., Hensarling, T. P. and Yatsu, L. Y. (1972). Cucurbit seeds: I. Characterizations and its uses of oils and proteins, a review. Economics and Botany, 26: 135-141.
Jiao, D., Jiang, Q., Liu, Y. and Ji, L. (2019). Nephroprotective effect of wogonin against cadmium-induced nephrotoxicity via inhibition of oxidative stress-induced MAPK and NF-kB pathway in Sprague Dawley rats, Human and Experimental Toxicology, 38: 1082–1109.
Jin, W., Xue, Y., Xue, Y., Han, X., Song, Q. and Zhang, J. (2020). Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity, contribution of NF-κB and Nrf2 pathways, Biomedicine and Pharmacotherapy, 126: 110047.
Kandemir, F. M., Kucukler, S., Caglayan, C., Gur, C., Batil, A. A. and Gülçin, I. (2017). Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties. Journal of Food Biochemistry, 41: 12398.
Kate, A. E., Lohani, U. C., Pandey, J. P., Shahi, N.C. and Sarkar, A. (2014). Traditional and mechanical method of the oil extraction from wild apricot kernel: a comparative study. Research Journal of Chemistry and. Environmental Science, 2(2): 54-60.
Kaur, S. and Sadwal, S. (2019). Studies on the phytomodulatory potential of fenugreek (Trigonella foenum-graecum) on bisphenol-A induced testicular damage in mice. Andrology, 52: e13492.
Li, Y-J., Song, T-B., Cai, Y-Y., Zhou, J-S., Song, X., Zhao, X. and Wu, X-L. (2009). Bisphenol A Exposure Induces Apoptosis and Upregulation of Fas/FasL and Caspase-3 Expression in the Testes of Mice. Toxicological Sciences, 108(2): 427–436.
Mathur, P. P, Saradha, B., and Vaithinathan, S. (2008). Impact of environmental toxicants on testicular function. Immunology Endocrine Metabolic Agents of Medical Chemistry 8: 79–90.
Moraes, V. W. R., Caires, A. C. F., Paredes-Gamero, E. J., and Rodrigues, T. (2013). Organopalladium compound 7b targets mitochondrial thiols and induces caspase-dependent apoptosis in human myeloid leukemia cells. Cell Death Diseases, 4: 1–8.
Nna, V. U., Ujah, G. A., Mohamed, M., Etim, K. B., Igba, B. O., Augustine, E. R. and Osima, E. E. (2017). Cadmium chloride-induced testicular toxicity in male Wistar rats; prophylactic effect of quercetin, and assessment of testicular recovery following cadmium chloride withdrawal, Biomedical Pharmacotherapy, 94: 109–123.
OECD. (2008). Acute Oral Toxicity Testing Procedures. http://www.oecd.org/env/testguidelines.
Ogunbusola, E. M., Fagbemi, T. N., and Osundahunsi, O. F. (2010). Amino acid composition and protein quality of white melon (Cucumeropsis mannii) flour, Nigerian Food Journal, 28(1): 14–21.
Ohkawa, H., Ohishi, N., and Yagi, K. (1979). Assay for lipid peroxides in animal tissues by the thiobarbituric acid reaction. Annals of Biochemistry, 95: 351–358.
Ohore, O. E., and Songhe, Z. (2019). Endocrine-disrupting effects of bisphenol A exposure and recent advances on its removal by water treatment systems-A review. Scientific African, 5: e00135.
Othman, A. I., Edrees, G. M., El-Missiry, M. A. Ali, D. A., Aboel-Nour, M. and Dabdoub, B. R. (2016). Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity. Toxicology and Industrial Health, 32: 1537–1549.
Paglia, D. E., and Valentine, W. M. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory & Clinical Medicine, 70: 158–69.
Park, B., Kwon, J. E., Cho, S. M., Kim, C. W., Lee, D. E., Koo, Y. T., Lee, S. H., Lee, H. M. and Kang, S. C. (2018). Protective effect of Lespedeza cuneata ethanol extract on Bisphenol A-induced testicular dysfunction in vivo and in vitro. Biomedicine and Pharmacotherapy, 102: 76–85.
Rehman, K., Munawar, S. M., Akash, M. S., Buabeid, M. A., Chohan, T. A., and Tariq, M. (2020). Hesperidin improves insulin resistance via downregulation of inflammatory responses: biochemical analysis and in silico validation. PLoS One, 15: 0227637.
Resim, S., Kurutas, E. B., Gul, A. B., Eren, M., Benlioglu, C., Efe, E. and Atli. Y. (2015). The Levels of Oxidative Stress Biomarkers in Rats as a Response to Different Techniques of Testicular Biopsy. Indian Journal of Surgery, 77(2): 310-313.
Ribeiro, T. P., Fonseca, F. L., de Carvalho, M. D., Godinho, R. M., de Almeida, F. P., Saint’Pierre, T. D., Rey, N. A., Fernandes, C., Horn, A. and Pierre, M. D. (2017). Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend the life span of Saccharomyces cerevisiae. Biochemical Journal, 474(2): 301-315.
Tamilselvan, P., Bharathiraja, K., Vijayaprakash, S. and Balasubramanian, M. P. (2013). Protective role of lycopene on bisphenol A-induced changes in sperm characteristics, testicular damage, and oxidative stress in rats. International Journal of Pharmacy and Biological Science, 4: 131–143.
Tsai, D. S., Huang, M. H., Tsai, J. C., Chang, Y. S., Chiu, Y. J., Lin, Y. C., Wu, L.Y., Peng, W. H. (2015). Analgesic
and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice. Journal of Medicinal Food, 18(5): 592-600.
Wang, H., Ding, Z., Shi, Q. M., Ge, X., Wang, H. X., Li, M. X., Chen, G., Wang, Q., Ju, Q. and Zhang, J. P. (2017). Anti-androgenic mechanisms of Bisphenol A involve androgen receptor signaling pathways. Toxicology, 387: 10–16.
Wang, J., Chen, C., Jiang, Z., Wang, M., Jiang, H. and Zhang, X. (2016). Protective effect of Cordyceps militaris extracts against bisphenol A-induced reproductive damage. System Biology and Reproductive Medicine, 62: 249–257.
Wang, L., He, T., Fu, A., Mao, Z., Yi, L., Tang, S. and Yang, J. (2018). Hesperidin enhances angiogenesis via modulating expression of growth and inflammatory factor in diabetic foot ulcers in rats. European Journal of Inflammation, 20: 1–13.
Wu, H.-J., Liu, C., Duan, W.-X., Xu, S.-C., He, M.-D., Chen, C.-H.; Wang, Y.; Zhou, Z.; Yu, Z.-P.; Zhang, L. (2013). Melatonin ameliorates bisphenol A-induced DNA damage in the germ cells of adult male rats. Mutation Research in Toxicology and Environmental Mutagenesis, 752: 57–67.
Yan, N., Wen, D.-S., Zhao, Y.-R. and Xu, S.-J. (2018). Epimedium sagittatum inhibits TLR4/MD-2 mediated NF-κB signaling pathway with anti-inflammatory activity, BMC Complementary and Alternative Medicine, 18: 303–311.
Zhang, Y., Han, L., Yang, H., Pang, J., Li, P., Zhang, G., Li, F., and Wang, F. (2017). Bisphenol A affects cell viability involved in autophagy and apoptosis in goat testis Sertoli cells. Environmental Toxicology and Pharmacology, 2832: 13-25.
How to Cite
Copyright (c) 2022 Dr. Aja, Peter Chinedu Agu, Hilary Akobi Ogwoni, Ugbala Ezebuilo Ekpono, Ernest Mbamalu Ezeh, Onyedika Gabriel Ani, Atamgba Agbor Asuk, Joshua Nonso Awoke, Boniface Anthony Ale, Felix Emmanuel Nwite, Oliver Ugochukwu Ukachi, Obasi Uche Orji, Peter Chinonso Nweke, Ugbala Ejike Ekpono, Gift Onyinye Ewa, Ikechuku Okorie Igwenyi, Esther Ugo Alum, Darlington Chiadikaobi Chukwu, Ekenechukwu Maduagwuna, , Francisca Chidimma. Nwiziogo
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.