Pharmacological Evaluation of Polyherbal Formulation for Nephroprotective Activity
Keywords:Acute Toxicity, Antioxidant, Gentamicin, Nephroprotective, Polyherbal Formulation
AbstractThe kidney plays an essential role in removing waste products and drugs from the body and maintaining balanced body fluids. It gets affected due to many factors, notably, diabetes and high blood pressure. Nowadays, naturally, derived products are essential in curing various ailments and are safe and cost-effective. The purpose of this study is to assess the toxicity profile and nephroprotective effect of a proprietary polyherbal formulation in Wistar albino rats for gentamicin-induced nephrotoxicity. The Polyherbal formulation was procured from Rumi Herbals Private Limited. Acute toxicity experiments were conducted in Wistar rats using the Gentamicin induced nephrotoxicity model as per OECD standards 423, and the efficacy was assessed using the Gentamicin induced nephrotoxicity model. The formulation was proven safe up to 2000mg/kg orally in an acute toxicity study, with no behavioral abnormalities and no fatality. The gentamicin 80 mg/kg i.p for 7 days induced nephrotoxicity in rats showed a significant (P<0.05) increase in the renal parameters and reduction in antioxidant levels compared with day 0. Whereas test drug-treated groups at a low dose (200 mg/kg) and high dose (400 mg/kg) showed significant (P<0.05) reduction in elevated renal parameters and improvement in antioxidant levels compared with the disease control group. According to the histopathological interpretation of isolated kidneys, this formulation protects from kidney damage and restores typical kidney architecture. From the results, the proprietary polyherbal formulation has shown effective nephroprotective activity may be due to the presence of secondary metabolites/phytoconstituents. Further investigation is essential to focus on the mechanism involved and standardize the active phytoconstituents responsible for the nephroprotective activity.
Malik HMA. Treatment through herbs. Medicinal plants of Pakistan. 2001; 6(3):21–3.
Sigerist HE . A history of medicine, Volume I, Oxford University Press, London; 1951. p. 47–9.
California. European markets for urinary stone removal devices and equipment report. Life Science Intelligence. 2008:453.
Boneses RN, Taussk HA. On the colorimetric determination of creatinine by the Jaffe reaction. J Biol Chem. 1945; 158:581–91. https://doi.org/10.1016/S0021-9258(19)51334-5
Natelson S. Micro-techniques of clinical chemistry for the routine laboratory. Spring-Field, Illinois; 1957. p. 381.
Fossati P, Prencipe L, Berti G., Use of 3, 5-dichloro- 2-hydroxy benzene sulfonic and/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clin Chem. 1980; 26:227–31. https://doi.org/10.1093/clinchem/26.2.227. PMid:7353268
Fawcett JK, Scott JE. A rapid and precise method for the determination of urea. J Clin Pathol. 1960; 13(2):156–9. https://doi.org/10.1136/jcp.13.2.156. PMid:13821779. PMCid:PMC480024
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ., Protein measurement with the Folin’s reagent. J Biol Chem. 1951, 193:26–76. https://doi.org/10.1016/S0021-9258(19)52451-6
Doumas BT, Biggs HG, Arends RL, Pinto PVC. Determination of Serum Albumin. Based on the methods of Rodkey (1), Bartholomew and Delaney (2), and Doumas, Watson, and Biggs (3)., Editor(s): Gerald R. Cooper, Standard Methods of Clinical Chemistry, Elsevier, Volume 7; 1972. p. 175–88. https://doi.org/10.1016/B978-0-12-609107-6.50022-2
Maruna RF, Jrinder SR. Determination of serum sodium by colorimetric method. Clin Chem. 1958.
Maruna RFL., Determination of serum potassium by colorimetric method. Clinicachemicaacta. 1957; 2(2):131–3. https://doi.org/10.1016/0009-8981(57)90093-1
Fiske CH, Subbarrow. The colorimetric determination of phosphorus. J Biol Chem. 1925; 66:375–400. https://doi.org/10.1016/S0021-9258(18)84756-1
Dacie JV, Lewis SM. Practical Haematology, 4th edition J and A, Churchill, UK; 1968. p. 37.
Beuge JA, Aust SD. The thiobarbituric acid assay. Meth Enzymol. 1978; 52:306–7.
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984; 21(2):130–2.
Beers R, Sizer I. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952; 195:133–42. https://doi.org/10.1016/S0021-9258(19)50881-X
Rotruck JT, Pope AL, Ganther HE. Selenium: Biochemical roles as component of glutathione peroxidase. Science. 1973; 179:588–90. https://doi.org/10.1126/science.179.4073.588. PMid:4686466
Moron MS, Dse Pierre JW, Manerwik KB. Levels of glutathione, glutathione reductase and glutathione-s-transferase activities in rat lung and liver. Biochim Biophys Acta. 1978, 582:67–8. https://doi.org/10.1016/0304-4165(79)90289-7
Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AA, Vernekar SN. Markers of renal function tests. N Am J Med Sci. 2010; 2(4):170–3.
Weiner ID, Mitch WE, Sands JM. Urea and ammonia metabolism and the control of renal nitrogen excretion. Clin J Am Soc Nephrol. 2015; 7;10(8):1444–58. https://doi.org/10.2215/CJN.10311013. PMid:25078422. PMCid:PMC4527031
De Oliveira EP, Burini RC. High plasma uric acid concentration: Causes and consequences. Diabetol Metab Syndr. 2012; 4:12. https://doi.org/10.1186/1758-5996-4-12. PMid:22475652. PMCid:PMC3359272
Martin WF, Armstrong LE, Rodriguez NR. Dietary protein intake and renal function. Nutr Metab (Lond). 2005; 20; 2:25. https://doi.org/10.1186/1743-7075-2-25. PMid:16174292. PMCid:PMC1262767
Hermann, Janice R. Protein and the Body (PDF). Oklahoma Cooperative Extension Service, Division of Agricultural Sciences and Natural Resources. Oklahoma State University. p. T-3163-1–4.
Gounden V, Vashisht R, Jialal I. Hypoalbuminemia. 2021. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. PMID: 30252336.
Busher JT. Serum albumin and globulin. In: Walker HK, Hall WD, Hurst JW, (editors). Clinical methods: The history, physical, and laboratory examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 101.
Padugupati S, Kumar KK, Vasantha L, Sarma D. Study of serum protein and electrophoretic pattern in pumonarytuberculosis patients. Int J Clin Biochem Res. 2018; 5(3):353–60 https://doi.org/10.18231/2394-6377.2018.0074
Strazzullo P, Leclercq C. Sodium. Adv Nutr. 2014; 1; 5(2):188–90. https://doi.org/10.3945/an.113.005215. PMid:24618759. PMCid:PMC3951800
Clase CM, Carrero JJ, Ellison DH, Grams ME, Hemmelgarn BR, Jardine MJ, et al. Potassium homeostasis and management of dyskalemia in kidney diseases: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2020; 97(1):42–61. https://doi.org/10.1016/j.kint.2019.09.018. PMid:31706619
Fourtounas C. Phosphorus metabolism in chronic kidney disease. Hippokratia. 2011; 5(Suppl 1):50–2.
Obeagu, Emmanuel. Erythropoietin and Kidney Diseases: A Review. 2016; 33:760–92.
Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014. https://doi.org/10.1155/2014/360438. PMid:24999379. PMCid:PMC4066722
Younus H. Therapeutic potentials of superoxide dismutase. Int J Health Sci (Qassim). 2018; 12(3):88–93.
Nandi A, Yan LJ, Jana CK, Das N. Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxid Med Cell Longev. 2019; 11. https://doi.org/10.1155/2019/9613090. PMid:31827713. PMCid:PMC6885225
Altuhafi A, Altun M, Hadwan MH. The correlation between selenium-dependent glutathione peroxidase activity and oxidant/antioxidant balance in sera of diabetic patients with nephropathy. Rep Biochem Mol Biol. 2021; 10(2):164–72. https://doi.org/10.52547/rbmb.10.2.164. PMid:34604406. PMCid:PMC8480288
Lushchak, Volodymyr. Glutathione homeostasis and functions: Potential targets for medical interventions. J Amino Acids. 2012. https://doi.org/10.1155/2012/736837. PMid:22500213. PMCid:PMC3303626