Effects of Cobalamin (Vitamin B₁₂) on Gentamicin Induced Nephrotoxicity in Rat

 

 Buy Article Permissions and Reprints

Abstract

Background The main side effect of gentamicin is nephrotoxicity. The effect of cobalamin (Cob) was investigated on gentamicin nephrotoxicity in rats.

Methods Renal injury induced by i.p. injection of gentamicin (100 mg/kg) for 8 consecutive days. Cobalamin (6 mg/kg/day, i.p) treatment was done for 8 consecutive days as co-treatment and post-treatment protocol.

Results Cobalamin significantly increased creatinine clearance levels and renal blood flow which were reduced by gentamicin. Also, cobalamin significantly improved serum electrolytes (sodium and potassium) levels which were disturbed by gentamicin. Cobalamin significantly compensated deficits in the antioxidant defense mechanisms, suppressed lipid per oxidation and ameliorated renal tissue damage mediated by gentamicin.

Conclusion The results of the current study indicated that cobalamin effectively protected the kidney tissue against gentamicin induced acute nephrotoxicity in rats. The antioxidant and anti-inflammatory activities can be supposed the main factors responsible for the nephroprotective effect of cobalamin.

• References

• 1 Lopez-Novoa JM, Quiros Y, Vicente L. et al. New insights into the mechanism of aminoglycoside nephrotoxicity: An integrative point of view. Kidney international 2011; 79: 33-45
  CrossrefPubMedSearch in Google Scholar
• 2 Dirkes S. Acute kidney injury: Not just acute renal failure anymore?. Critical Care Nurse 2011; 31: 37-50
  CrossrefPubMedSearch in Google Scholar
• 3 Beauchamp D, Labrecque G. Aminoglycoside nephrotoxicity: Do time and frequency of administration matter?. Current Opinion in Critical Care 2001; 7: 401-408
  CrossrefPubMedSearch in Google Scholar
• 4 Ahmed MF, Elashheb MS, Rabha FMB. Protective effect of l-carnitine against gentamicin-induced nephrotoxicity in rats. World academy of science, engineering and technology, international journal of medical, health, biomedical, bioengineering and pharmaceutical engineering 2015; 7: 767-772
  PubMedSearch in Google Scholar
• 5 Ajami M, Eghtesadi S, Pazoki-Toroudi H. et al. Effect of crocus sativus on gentamicin induced nephrotoxicity. Biological research 2010; 43: 83-90
  PubMedSearch in Google Scholar
• 6 Banday AA, Farooq N, Priyamvada S. et al. Time dependent effects of gentamicin on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in rat kidney tissues. Life sciences 2008; 82: 450-459
  CrossrefPubMedSearch in Google Scholar
• 7 Morales AI, Buitrago JM, Santiago JM. et al. Protective effect of trans-resveratrol on gentamicin-induced nephrotoxicity. Antioxidants and Redox Signaling 2002; 4: 893-898
  CrossrefPubMedSearch in Google Scholar
• 8 Baliga R, Ueda N, Walker PD. et al. Oxidant mechanisms in toxic acute renal failure. Drug metabolism reviews 1999; 31: 971-997
  CrossrefPubMedSearch in Google Scholar
• 9 Martinez-Salgado C, Lopez-Hernandez FJ, Lopez-Novoa JM. Glomerular nephrotoxicity of aminoglycosides. Toxicology and applied pharmacology 2007; 223: 86-98
  CrossrefPubMedSearch in Google Scholar
• 10 Patzer L. Nephrotoxicity as a cause of acute kidney injury in children. Pediatric Nephrology. 2008; 23: 2159-2173
  CrossrefPubMedSearch in Google Scholar
• 11 Wheatley C. A scarlet pimpernel for the resolution of inflammation? The role of supra-therapeutic doses of cobalamin, in the treatment of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic or traumatic shock. Medical hypotheses 2006; 67: 124-142
  CrossrefPubMedSearch in Google Scholar
• 12 Abeles RH, Dolphin D. The vitamin B12 coenzyme. Accounts of Chemical Research 1976; 9: 114-120
  CrossrefPubMedSearch in Google Scholar
• 13 Randaccio L, Geremia S, Demitri N. et al. Vitamin B12: Unique metalorganic compounds and the most complex vitamins. Molecules 2010; 15: 3228-3259
  CrossrefPubMedSearch in Google Scholar
• 14 Moreira ES, Brasch NE, Yun J. Vitamin B 12 protects against superoxide-induced cell injury in human aortic endothelial cells. Free Radical Biology and Medicine. 2011; 51: 876-883
  CrossrefPubMedSearch in Google Scholar
• 15 Birch CS, Brasch NE, McCaddon A. et al. A novel role for vitamin B 12: Cobalamins are intracellular antioxidants in vitro. Free Radical Biology and Medicine. 2009; 47: 184-188
  CrossrefPubMedSearch in Google Scholar
• 16 Patil CR, Jadhav RB, Singh PK. et al. Protective effect of oleanolic acid on gentamicin induced nephrotoxicity in rats. Phytotherapy Research. 2010; 24: 33-37
  CrossrefPubMedSearch in Google Scholar
• 17 Caram-Salas NL, Reyes-García G, Medina-Santillan R. et al. Thiamine and cyanocobalamin relieve neuropathic pain in rats: Synergy with dexamethasone. Pharmacology 2006; 77: 53-62
  CrossrefPubMedSearch in Google Scholar
• 18 Whitesall SE, Hoff JB, Vollmer AP. et al. Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods. American Journal of Physiology-Heart and Circulatory Physiology. 2004; 286: H2408-H2415
  CrossrefPubMedSearch in Google Scholar
• 19 Ahmadi M, Hajihashemi S, Chehrei A. et al. Therapeutic effects of Urtica dioica methanolic extrat on gentamicine induced nephrotoxicity. Koomesh 2014; 15: 220-231
  PubMedSearch in Google Scholar
• 20 Ameen NMA, Altubaigy F, Jahangir T. et al. Effect of Nigella sativa and bee honey on pulmonary, hepatic and renal function in Sudanese in Khartoum state. Journal of Medicinal Plants Research 2011; 5: 6857-6863
  PubMedSearch in Google Scholar
• 21 Vallon V, Rose M, Gerasimova M. et al. Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus. American Journal of Physiology-Renal Physiology. 2013; 304: F156-F167
  PubMedSearch in Google Scholar
• 22 Laustsen C, Østergaard JA, Lauritzen MH. et al. Assessment of early diabetic renal changes with hyperpolarized [1–13C] pyruvate. Diabetes/metabolism Research and Reviews 2013; 29: 125-129
  CrossrefPubMedSearch in Google Scholar
• 23 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 1979; 95: 351-358
  CrossrefPubMedSearch in Google Scholar
• 24 Benzie IF, Strain J. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Analytical biochemistry 1996; 239: 70-76
  CrossrefPubMedSearch in Google Scholar
• 25 Al-Shabanah OA, Aleisa AM, Al-Yahya AA et al. Increased urinary losses of carnitine and decreased intramitochondrial coenzyme A in gentamicin-induced acute renal failure in rats. Nephrology Dialysis Transplantation. 2009 gfp457
  PubMed
• 26 Ali BH, Za’abi A, Blunden G. et al. Experimental Gentamicin Nephrotoxicity and Agents that Modify it: A Mini-Review of Recent Research. Basic & clinical pharmacology & toxicology 2011; 109: 225-232
  CrossrefPubMedSearch in Google Scholar
• 27 Randjelovic P, Veljkovic S, Stojiljkovic N. et al. Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI J. 2017; 16: 388-399
  PubMedSearch in Google Scholar
• 28 Roth JR, Lawrence JG, Rubenfield M. et al. Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium. Journal of bacteriology 1993; 175: 3303-3316
  CrossrefPubMedSearch in Google Scholar
• 29 Wheatley C. The return of the Scarlet Pimpernel: Cobalamin in inflammation II–cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS. Journal of nutritional & environmental medicine 2007; 16: 181-211
  CrossrefPubMedSearch in Google Scholar
• 30 Sorribas V, Halaihel N, Puttaparthi K. et al. Gentamicin causes endocytosis of Na/Pi cotransporter protein (NaPi-2). Kidney international 2001; 59: 1024-1036
  CrossrefPubMedSearch in Google Scholar
• 31 Park JW, Bae EH, Kim IJ. et al. Renoprotective effects of paricalcitol on gentamicin-induced kidney injury in rats. American Journal of Physiology-Renal Physiology. 2010; 298: F301-F313
  PubMedSearch in Google Scholar
• 32 Thounaojam MC, Jadeja RN, Devkar RV. et al. Sida rhomboidea. Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats. Journal of Ethnopharmacology 2010; 132: 365-367
  CrossrefPubMedSearch in Google Scholar
• 33 Walker PD, Barri Y, Shah SV. Oxidant mechanisms in gentamicin nephrotoxicity. Renal Failure 1999; 21: 433-442
  CrossrefPubMedSearch in Google Scholar
• 34 Couto GK. Estudo da Função em Artérias de Resistência de Ratos Pós-infarto do Miocárdio. Universidade de São Paulo; 2012
  Search in Google Scholar
• 35 Giaccia AJ, Simon MC, Johnson R. The biology of hypoxia: The role of oxygen sensing in development, normal function, and disease. Genes & Development 2004; 18: 2183-2194
  CrossrefPubMedSearch in Google Scholar
• 36 Seetharam B. Receptor-mediated endocytosis of cobalamin (vitamin B12). Annual Review of Nutrition 1999; 19: 173-195
  CrossrefPubMedSearch in Google Scholar
• 37 Hosseinzadeh H, Moallem S, Moshiri M. et al. Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice. Arzneimittelforschung 2012; 62: 324-329
  Thieme ConnectPubMedSearch in Google Scholar
• 38 Romagnoli M, Gomez-Cabrera M-C, Perrelli M-G. et al. Xanthine oxidase-induced oxidative stress causes activation of NF-κB and inflammation in the liver of type I diabetic rats. Free Radical Biology and Medicine. 2010; 49: 171-177
  CrossrefPubMedSearch in Google Scholar
• 39 Sánchez-López E, Rayego S, Rodrigues-Díez R. et al. CTGF promotes inflammatory cell infiltration of the renal interstitium by activating NF-κB. Journal of the American Society of Nephrology. 2009; 20: 1513-1526
  CrossrefPubMedSearch in Google Scholar
• 40 Tugcu V, Ozbek E, Tasci AI. et al. Selective nuclear factor κ-B inhibitors, pyrolidium dithiocarbamate and sulfasalazine, prevent the nephrotoxicity induced by gentamicin. BJU International 2006; 98: 680-686
  CrossrefPubMedSearch in Google Scholar
• 41 Ozbek E, Cekmen M, Ilbey YO. et al. Atorvastatin prevents gentamicin-induced renal damage in rats through the inhibition of p38-MAPK and NF-kB pathways. Renal Failure 2009; 31: 382-392
  CrossrefPubMedSearch in Google Scholar
• 42 Volpini R, Balbi A, Costa R. et al. Increased expression of p38 mitogen-activated protein kinase is related to the acute renal lesions induced by gentamicin. Brazilian Journal of Medical and Biological Research 2006; 39: 817-823
  CrossrefPubMedSearch in Google Scholar