Myelosuppression and Nephrotoxicity Induced by Cisplatin in Female Rats: The Role of Berberine Nanoparticles

  • Nema Abdelhameed Mohamed Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt
Keywords: Berberine Nanoparticles, Cisplatin, Nephrotoxicity, Female Rats

Abstract

Cisplatin (CDDP) is one of the most effective antineoplastic drugs used in chemotherapy, strategies to protect tissues against cisplatin nephrotoxicity is a clinical interest. This study aimed to evaluate the possible protective effect of berberine nanoparticles (BBR-NPs) against cisplatin-induced nephrotoxicity in female rats. Intraperitoneal (IP) injection of cisplatin (8 mg/kg) caused significant decrease in RBC, Hb, Hct, WBC and platelets. Also, cisplatin caused disturbances in kidney function as documented by a significant increase in urea, uric acid, creatinine and MDA, with significant decreases in the total protein, albumin, GSH and total thiol.TNF- 7556_a.png, caspase-3, IL-2, IL-6 and IL-17556.pngwere increased in cisplatin treated group. The histopathological changes in cisplatin group include degeneration and desquamation of tubular epithelial cells, hyaline cast formation, inflammatory cell infiltration and tubular dilation. Oral administration of BBR-NPs at a dose 1mg/kg/day for 30 days after cisplatin produced significant decrease in the levels of urea, uric acid, creatinine, TNF- 7556_a.pngand caspase-3 as well as kidney MDA with a marked increase in total protein, albumin, GSH, total thiol and repairing the histopathological changes. Scanning microscope of RBC showed the protective effect of BBR-NPs against the different changes induced by CDDP. The present study suggested that the anti-oxidant and anti-inflammatory effects of BBR-NPs may prevent CDDP-induced nephrotoxicity via decreasing the oxidative stress, inhibiting the inflammation and apoptosis.

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Ivana, ST., Branka, IO., Nataza, Z., Ordevici, S., Markovici, A., Štajni, G., Zorica, S. and Saicic, C. (2010). Effects of cisplatin on lipid peroxidation and the glutathione redoxstatus in the liver of male rats. The protective role of selenium. Arch. Biol. Sci., Belgrade, 62 (1), 75-82.

Sooriyaarachchi, M., White, WM., Narendran, A. and Gailer, J. (2014). Metallomics. Integrated Biometal Science, 6, 532–541.

Chvalova, K., Brabec, V. and Kašparkova, J. (2007). The mechanism of the formation of DNA-protein cross-links by antitumor cisplatin. Nucleic Acids Res., 35, 1812–1821.

Fuertes, MA., Alonso, C. and Perez, JM. (2003). Biochemical modulation of cisplatin mechanisms of action: enhancement of antitumor activity and circumvention of drug resistance. Chem. Rev., 103, 645–662.

Miller, RP., Tadagavadi, RK. And Ramesh. (2010). Mechanisms of cisplatin nephrotoxicity. Toxins (Basel), 2, 2490–2518.

Tietz, R., Lyer, S., Dürr, S. and Alexiou, C. (2015). Nanoparticles for cancer therapy using magnetic forces. Nanomedicine, 7(3), 447-457.

Sagadevan, S., Savitha, S. and Preethi, R. (2014). Beneficial Applications of Nanoparticles in Medical Field-A Review. Int. J. PharmTech. Res., 6(5), 1711-1717.

Ortiz, LM., Lombardi, P., Tillhon, M. and Scovassi, AI. (2014). Berberine, an epiphany against cancer. Molecules, 19(8), 12349-12367.

Zou, K., Zhao, L., Yong, Z., Hao-yue, Z., Bo, L., Wei-liang, Z., Ji-ye, S., Qi, J. and Yi-ming, L. (2017). Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacologica Sinica, 38, 157–167

Heidarian, E., Rafieian-Kopaei, M., Khoshdel, A. and Bakhshesh, M. (2014). Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: An additional mechanism for the hypolipidemic effects of berberine. Asian. Pac. J. Trop. Biomed., 4(1), 429–435.

Wu, Q., Tang, ZH., Peng, J., Liao, L., Pan, LH., Wu, CY., Jiang, ZS., Wang, GX. and Liu LS. (2014). The dual behavior of PCSK9 in the regulation of apoptosis is crucial in Alzheimer’s disease progression. Biomed. Rep., 2, 167–171.

Li, G., Sha, SH., Zotova, E., Arezzo, J., Van de Water, T. and Schacht, J. (2002). Salicylate protects hearing and kidney function from cisplatin toxicity without compromising its oncolytic action. Lab Invest., 82, 585-596.

Mohamed, NA., Awatef, MA., Doaa, AG., Adham, RM. and Yassmin, ME. (2018). The curative effect of berberine nanoparticles and cisplatin combination therapies against hepatocarcinogenesis-induced by n-nitroso-diethylamine in male rat. Journal of Advances in Biology, 11(1), 2180-2200.

Vermorken, JB., Van Der, VWJF., Klein I, Gall, HE. and Pinedo, HM. (1982). Pharmacokienetic of free platinum species following rapid, 3-hrs and 24 hrs infusions of cis -diammine dicholoroplatinium (II) and its therapeutic implication. Eut Cancer Clin Oncolo, 18(11), 1069-1074.

Ghareeb, D., Amarry, H., Hafez, H., Hussien, H., Abd-Elmegied, A. and Abd EL-Moneam, N. (2013). In vivo biochemical and molecular characterization of anti-acetylcholinesterase berberine as amyloid precursor protein translation blocker for Alzheimer's disease treatment. Neuro Degenerative Disease, 11 (Suppl 1).

Henry, RJ. (1974). Clinical chemistry, principles and techniques, (2nd Ed). Harper and Row, Hagerstown MD. Lange medical publication. California, 819-831.

Patton, CJ. and Crouch, SR. (1977). Spectrophotometric and kinetics investigation of the Berthelot reaction for the determination of ammonia. Anal Chem, 49, 464–469.

Gornall, AJ., Bardawill, CJ. and David, MM. (1949). Determination of serum proteins by means of the biuret reaction. J. Biol. Chem., 177, 751-66.

Doumas, BT., Watson, WA. and Biggs, HG. (1971). Albumin standards and the measurement of serum albumin with bromcresol green. Clinica Chimica Acta, 31, 87-96.

Ohkawa, H., Ohishi, N. and Yagi, K. (1979). Analytical biochemistry, Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry, 95, 351-358.

Jollow, DJ., Mitchell, JR., Zampaglione, N. and Gillete, JR. (1974). Bromobenzene-induced liver necrosis, Protective role of glutathione and evidence for 3,4-bromobenzeneoxide as the hepatotoxic metabolite. Pharmacol, 11, 151-169.

Sedlak, J. and Lindsay, RH. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem., 25, 192-205.

Ferguson-Smith, AC., Chen, YF., Newman, M.S., May, LT., Sehgal, PB. and Ruddle, FH. (1988). Regional localization of the interferon-?2B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21. Genomics, 2, 203-208.

Wu, B., Ootani, A., Iwakiri, R., Sakata, Y., Fujise, T., Amemori, S., Yokoyama, F. and et al. (2006). T cell deficiency leads to liver carcinogenesis in Azoxymethane-treated rats. Exp Biol Med., 231, 91-8.

Bancroft, D. and Gamble, M. The theory and practice of histological technique. 5th Ed. Churchill, Living Stone: Elsevier, 2002, 75.

Ashraf, YN. (2014). Protective effect of aged garlic extract against the oxidative stress induced by cisplatin on blood cells parameters and hepatic antioxidant enzymes in rats. Toxicol Rep., 1, 682-91.

Mohamed, HE., El-Swefy, SE., Mohamed, RH., Amal, MH. and Ghanim, AM. (2013). Effect of erythropoietin therapy on the progression of cisplatin induced renal injury in rats. Exp Toxicol Pathol., 65, 197-203.

Florea, AM., and Büsselberg, D. (2011). Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers, 3(1), 1351-1371.

Olas, B., Wachowicz, B., Majsterek, I. and Blasiak J. (2005). Resveratrol may reduce oxidative stress induced by platinum compounds in human plasma, blood platelets and lymphocytes. Anticancer Drugs, 16, 659–65.

Kim, HS., Hyeong-Geug, K., Hwi-Jin, I., Jin-Seok, L., Sung-Bae, L., Won-Yong, K., Hye-Won, L., Sam-Keun, L. and Chang KB. and Chang-Gue, S. (2017). Antiemetic and myeloprotective effects of rhus verniciflua stoke in a cisplatin-induced rat model. Evidence-Based Complementary and Alternative Medicine, 2017, 10 pages.

Chandirasegaran, G., Elanchezhiyan, C., Kavisa G. and Hemalatha, S. (2017). Protective role of berberine chloride on blood components in streptozotocin induced diabetic rats. Chemical and Pharmaceutical Research, 9(3), 69-73.

Yao, X., Panichpisal, K., Kurtzman, N. and et al. (2007). Cisplatin nephrotoxicity: a review. Am. J. Med. Sci., 334, 115–124.

Dasari, S. and Tchounwou, PB. (2014). Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol., 740, 364–378.

Pabla1, N. and Dong, Z. (2008). Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies. Kidney Int., 73, 994–1007.

Alhoshani, AR., Mohamed, M., Hafez, Sufia H., Abdel Malek A., Moureq RA., Salim, SA., Musaad, A., Alshammari, MM. and Almutairi, OAA. (2017). Protective effect of rutin supplementation against cisplatin-induced nephrotoxicity in rats. BMC Nephrol., 18, 194.

Song, Z., Chang, H., Han, N., Liu, Z., Wang, Z., Gao, H. and Yin, J. (2017). He-Wei granules inhibit chemotherapy-induced vomiting (CINV) in rats by reducing oxidative stress and regulating 5-HT, substance P, ghrelin and obestatin. RSC Advances, 7(69), 43866-43878.

Adil, M., Kandhare, AD1., Dalvi, G., Ghosh, P., Venkata, S., Raygude, KS. and Bodhankar, SL. (2016 ). Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction. Ren Fail., 38(6), 996-1006.

El-Beshbishy, H., Bahashwan, S., Ali, H. and Fakher, H. (2011). Abrogation of cisplatin-induced nephrotoxicity in mice by alpha lipoic acid through ameliorating oxidative stress and enhancing gene expression of antioxidant enzymes. European Journal of Pharmacology, 668, 278-284.

Karasawa, T. and Steyger, PS. (2015). An integrated view of cisplatin-induced nephrotoxicity and ototoxicity. Toxicology Letters, 237(3), 219–227,

Lopez-Novoa, JM., Quiros, Y., Vicente, L. and et al. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity. An integrative point of view. Kidney Int., 79, 33–45.

Kruger, K., Thomale, J., Stojanovic, N., Osmak, M., Henninger, C., Bor-mann, S. and Fritz, G. (2015). Platinum-induced kidney damage: unraveling the DNA damage response (DDR) of renal tubular epithelial and glomerular endothelial cells following platinum injury. Biochim Biophys Acta, 1854, 685–698.

Ali, BH., Al Moundhri, MS., TagEldin, M., Nemmar, A. and Tanira, MO. (2007). The ameliorative effect of cysteine prodrug L-2-oxothiazolidine-4-carboxylic acid on cisplatin-induced nephrotoxicity in rats. Fundam Clin Pharmacol., 21, 547–553.

¨Ozkol, H., Musa, D., Tuluce, Y. and Koyuncu, I. (2012). Ameliorative influence of Urtica dioica L against cisplatin-induced toxicity in mice bearing Ehrlich ascites carcinoma. Drug and Chemical Toxicology, 35(3), 251–257.

Arivarasu, NA., Priyamvada, S. and Mahmood, R. (2013). Oral administration of caffeic acid ameliorates the effect of cisplatin on brush bordermembrane enzymes and antioxidant system in rat intestine. Experimental and Toxicologic Pathology, 65(1-2), 21-25.

Abdel-Wahab, AE., Doaa, AG., Eman, EMS., Marwa, MAS. and Maha, AED. (2013). In vitro biological assessment of berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complementary and Alternative Medicine, 13, 218.

Lao-ong, T., Waranya, C., Nobuo, N. and Kanokwan, J. (2012). Alteration of hepatic glutathione peroxidase and superoxide dismutase expression in streptozotocin-induced diabetic mice by berberine. Pharmaceutical Biology, 50(8), 1007-1012.

Domitrovic, R., Olga, C., Ester, P., Marko, Š., Lorena, M. and Z?eljka, CO. (2013). Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, in?ammation, autophagy and apoptosis. Food and Chemical Toxicology, 62, 397–406.

Wu, D., Wen, W., Qi, CL., Zhao, RX., Lu, JH., Zhong, CY. and Chen, YY. (2012). Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin. Phytomedicine, 19(8–9), 712–718.

Wang, FL., Tang, LQ., Yang, F., Zhu, LN., Cai, M. and Wei, W. (2013). Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats. Mol. Biol. Rep., 40(3), 2405–2418.

Oh, GS., Kim, HJ., Shen, A., Lee, SB., Yang, SH., Shim, H. and et al. (2016). New therapeutic concept of nad redox balance for cisplatin nephrotoxicity. Biomed Res Int., 2016, 4048390.

Ramesh, G. and Reeves, WB. (2004). Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-alpha. Kidney Int., 65, 490-499.

Dkhil, M.A., Mahmoud, SM. and Saleh, Q. (2017). Berberine improves the intestinal antioxidant status of laboratory mice, Mus musculus. Saudi Journal of Biological Sciences, 24(7), 1567-1573.

Yuna, F., Xie, Q., Wu, J., Bai, Y., Mao, B., Dong, Y., Bi, W., Ji, G., Tao, W., Wang, Y. and Yuan, Z. (2011). MST-1 promotes apoptosis through regulating sirt1-dependent p53 deacetylation. J. Biol. Chem., 286, 6940-6945.

Nho, JH., Ho-Kyung, J., Mu-Jin, L., Ji-Hun, J., Mi-Ok, S., Da-Eun, J., Hyun-Woo, CJ. and Choon, K. (2018). Beneficial effects of cynaroside on cisplatin-induced kidney injury In Vitro and In Vivo. Toxicol Res., 34(2), 133–141.

Mostafa, RE., Dalia, OS. and Dina, FM. (2018). Cisplatin-induced nephrotoxicity in rats: modulatory role of simvastatin and rosuvastatin against apoptosis and inflammation. Journal of Applied Pharmaceutical Science, 8(04), 043-050.

Meng, S., Lian-Sheng, W., Zhou-Qing, H., Qing, Z., Ying-Gang, S., Jia-Tian, C., Yi-Gang, L. and Chang-Qian, W. (2010). Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention. Clinical and Experimental Pharmacology and Physiology, 39, 406–411.

Lu, DY., Chih-Hsin, T., Yi-Hung, C. and I-Hua, W. (2010). Berberine suppresses neuroinflammatory responses through amp-activated protein kinase activation in bv-2 microglia. Journal of Cellular Biochemistry, 110, 697–705.

Al-Rejaie, SS., Abuohashish, HM., Alkhamees, OA., Aleisa, AM. and Alroujayee, AS. (2012). Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats. Lipids Health Dis., 11, 41.

Peng, CC., Hsieh, CL., Ker, YB., Wang, HY., Chen, KC. and Peng RY. (2012). Selected nutraceutic screening by therapeutic effects on doxorubicin-induced chronic kidney disease. Mol Nutr Food Res., 56(10), 1541–58.

Fujikawa, Y., Kawanishi, M., Kuraoka, I. and Yagi, T. (2014). Frequencies of mutagenic translesion DNA synthesis over cisplatin-guanine intra-strand crosslinks in lacZ plasmids propagated in human cells. Mutat Res Genet Toxicol Environ Mutagen, 770, 23–28.

Yu, W., Sheng, M., Xu, R. and et al. (2013). Berberine protects human renal proximal tubular cells from hypoxia/reoxygenation injury via inhibiting endoplasmic reticulum and mitochondrial stress pathways. Journal of Translational Medicine. 11, 24.

Wang, N., Yibin, F., Meifen, Z., Chi-Man, T., Kwan M., Yao, T. and Sai-Wah, T. (2010). Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: the cellular mechanism. J Cell Biochem., 111(6), 1426–1436.

Hosseinian, S., Hadjzadeh, MA., Roshan, NM., Khazaei, M., Shahraki, S., Mohebbati, R. and Rad, AK. (2018). Renoprotective effect of Nigella sativa against cisplatin-induced nephrotoxicity and oxidative stress in rat. Saudi J Kidney Dis Transpl., 29(1), 19-29.

Abdel-Aziz, AM., Mohamed, AI., Azza, AE., Nisreen, A., Tawab, O., Ayman, G. and Aly, A. (2018). Prophylactic effect of diacerein against cisplatin-induced nephrotoxicity in rats. Int. J. Pharmacol., 14, 384-390.

Published
2018-08-30
How to Cite
Mohamed, N. (2018). Myelosuppression and Nephrotoxicity Induced by Cisplatin in Female Rats: The Role of Berberine Nanoparticles. JOURNAL OF ADVANCES IN BIOLOGY, 11, 2218-2235. https://doi.org/10.24297/jab.v11i1.7556