Curcumin prevents tenofovir/lamivudine/efavirenzinduced nephrotoxicity in rats

Background and Aims: Nephrotoxicity is an adverse effect, which may occur with the use of tenofovir/lamivudine/efavirenz (TLE) in the treatment of human immune deficiency virus (HIV) infection. Curcumin (CUM), an isolate of Curcuma longa L. is used in folk medicine for the treatment of ailments. This study attempts to establish whether CUM supplementation can protect against a rat model of TLE-induced nephrotoxicity. Materials and Methods: Adult male Wistar rats (n=40) were randomly grouped and supplemented orally with CUM (50, 100 and 200 mg/kg/day) prior to the oral administration of TLE (300/300/600 mg/kg/day) for 30 days. After the treatment, the rats were fasted overnight, weighed and anesthetized. Blood samples were collected, and sera were extracted for biochemical analyses. Kidney samples were excised, weighed and processed for oxidative stress markers and histology. Results: Body weight was decreased (p<0.01) whereas kidney weight was increased (p<0.01) in TLE administered rats when compared to the control. Significant (p<0.001) increments in serum uric acid, creatinine, urea and kidney malondialdehyde levels were observed in TLE-administered rats. Significant (p<0.001) decreases in serum total protein, albumin, electrolytes, kidney superoxide dismutase, glutathione, catalase and glutathione peroxidase levels were observed in TLE administered rats when compared to the control. TLE produced tubular necrosis and hypercellular glomerulus with mesangial proliferation in the kidneys of treated rats. However, CUM (50, 100 and 200 mg/kg) supplementation abrogates TLE-induced nephrotoxicity in a dose-related manner at p<0.05, p<0.01 and p<0.001, respectively, when compared to TLE group. Conclusion: CUM seems effective against TLE-induced nephrotoxicity.

___

  • • Adikwu., E., & Apiakise W. (2016). Ameliorative effects of vitamins c and e on tenofovir/nevirapine-induced hepatorenal oxidative stress in albino rats. Indonesian Journal ofPharmacy, 27, 211–219.
  • • Aebi, H. (1974). Catalase in vitro. In S.P. Colowick & N. O. Kaplane (Eds.), Method in Enzymology (pp. 673-685). New York, USA: Academic Press.
  • • Akram, M., Uddin, S., Ahmed, A., Usmanghani, K., Hannan, A., Mohiuddi, E., & Asif, M. (2010). Curcuma longa and Curcumin: A Review Article. Romania Journal of Biology Plant Biology, 55, 65–70.
  • • Buege, J. A., & Aust, S. D. (1978). Microsomal lipid peroxidation. Methods in Enzymology, 52, 302–310. https://doi.org/10.1016/ S0076-6879(78)52032-6.
  • • El-Zawahry, B. H., & Abu El Kheir E. M. (2007). The min against gentamicin- induced renal dysfunction and Oxidative Stress in male albino rats. The Egyptian Journal of Hospital Medicine, 29, 546–556. https://doi.org/10.12816/EJHM.2007.17699
  • • Farghaly, H. S., & Hussein, M. A. (2010). Protective effect of curcumin against paracetamol-induced liver damage. AustralianJournal of Basic and Applied Sciences, 4(9), 4266–4274.
  • • Fernandez-Fernandez, B., Montoya-Ferrer, A., Sanz, A. B., Sanchez- Niño, M., Izquierdo, M. C., Poveda, J., & Aberto, O. (2011). Tenofovir Nephrotoxicity: 2011 Update. AIDS Research and Treatment, 2011, 1–11. https://doi.org/10.1155/2011/354908
  • • Gowda, S., Desai, P. B., Kulkarni, S. S., Hull, V. V., Math, A. A., & Vernekar, S. N. (2010). Markers of renal function tests. North American Journal of Medical Sciences, 2(4), 170–173.
  • • Herlitz, L.C., Mohan, S., Stokes, M. B., Radhakrishnan, J., D’Agati, V. D., & Markowitz, G.S. (2010). Tenofovir nephrotoxicity: Acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney International, 78(11), 1171–1177. https://doi.org/10.1038/ki.2010.318
  • • Hewlings, J. S., & Kalman, D. S. (2007). Curcumin. A Review of Its’ Effects on Human Health. Foods, 92, 2–11. https://doi.org/10.3390/ foods6100092
  • • Jang, E., Lee, J. K., Inn, K., Chung, E. K., Lee, K., & Lee, J. (2010). Renal Dysfunction and Tubulopathy Induced by High-Dose Tenofovir Disoproxil Fumarate in C57BL/6 Mice, Healthcare, 8, 417, 2–10. https://doi.org/10.3390/healthcare8040417
  • • Kalyesubula, R., & Perazella, M. A. (2016). Nephrotoxicity of HAART. AIDS Research and Treatment 2016, 1-11 https://doi. org/10.1155/2011/562790
  • • Lee, H., Kim, S., Lee G., Choi, M., Jung, H. , Kim Y. J. , Kwon, H. & Chae, H. (2016). Turmeric extract and its active compound, curcumin, protect against chronic CCl4-induced liver damage by enhancing antioxidation. BMC Complementary and Alternative Medicine, 16, 1–9. https://doi.org/10.1186/s12906-016-1307-6
  • • Lin, Y. G., Kunnumakkara, A. B., Nair, A., Merritt, W. M., Han, L. Y., Armaiz-Pena, G. N. … Sood, A. K. (2007). Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway. Clinical Cancer Research, 13, 3423– 3430. https://doi.org/10.1158/1078-0432.CCR-06-3072
  • • Menon, V. P., & Sudheer, A. R. (2007). Antioxidant and anti-inflammatory properties of curcumin. Advances in Experimental Medicine and Bioliogy, 595, 105–125. https://doi.org/10.1007/978-0- 387-46401-5_3
  • • Mohantya, I., Singh, A. D., Amit, D., Joshia. S., Keval, K.T., & Gupta, S. K., (2004). Protective effects of Curcuma longa on ischemia-reperfusion induced myocardial injuries and their mechanisms. Life Sciences, 75, 1701–1709. https://doi.org/10.1016/j.lfs.2004.02.032.
  • • Montaner, J. S. G., Wood, E., Kerr, T., Lima. V., Barrios, R., Shannon, K, ……Hogg R. (2010). Expanded highly active antiretroviral therapy coverage among HIV-positive drug users to improve individual and public health outcomes. Journal of Acquired Immune Deficiency Syndromes, 55(1), 5–9. https://doi.org/10.1097/ QAI.0b013e3181f9c1f0
  • • Nartey, E. T., Tetteh, R. A., Yankey, B. A., Nartey E. T., Lartey M., Leukens H. G. M., & Dodoo A. N. (2019). Tenofovir-associated renal toxicity in a cohort of HIV infected patients in Ghana. BMC Research Notes, 12, 2–6. https://doi.org/10.1186/s13104-019-4454-2
  • • Noorafshan, A., & Ashkani-Esfahani, S. (2013). Review of therapeutic effects of curcumin. Current Pharmaceutical Design, 19, 2032– 2046. https://doi.org/10.2174/1381612811319110006
  • • Palella, F. J, Jr., Delaney, K.M., Moorman, A. C., Loveless, M. O., Fuhrer, J., Satten G. A.,… Holmberg, S. D. (1998). Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. The New England Journal of Medicine, 338, 853–860. https:// doi.org/10.1056/NEJM199803263381301.
  • • Perazella, M. A. (2010). Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy. Kidney International, 78, 1060–1063. https://doi.org/10.1038/ki.2010.344
  • • Rotruck, J. T., Rope, A. L., Ganther, H. F., & Swason, A. B. (1973). Selenium: biochemical role as a component of glutathione peroxidase. Science, 179, 588–90. https://doi.org/10.1126/science. 179.4073.588
  • • Sedlak, J., & Lindsay, R. H. (1968). Estimation of Total, Protein- Bound, and Nonprotein Sulfhydryl Groups in Tissue with Ellman’s Reagent. Analytical Biochemistry, 25, 1192–1205. https://doi. org/10.1016/0003-2697(68)90092-4
  • • Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., & Srinivas, P. S. (1998). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica, 64, 353–356. https://doi.org/10.1055/s-2006-957450.
  • • Sun, M., & Zigman, S. (1978). An ImprovedSpectrophotometer Assay of Superoxide Dismutase Based On Epinephrine, Antioxidation. Analytical Biochemistry, 90, 81–89. https://doi. org/10.1016/0003-2697(78)90010-6
  • • World Health Organization (WHO) guidelines approved by the guidelines review committee, in consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. World Health Organization: Geneva. 2013.