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Effect of tocilizumab, an interleukin-6 inhibitor, on early stage streptozotocin-induced diabetic nephropathy in rats
- Source :
- Naunyn-Schmiedeberg's Archives of Pharmacology. 392:1005-1013
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- The aim of this study was to examine the effect of tocilizumab, an interleukin-6 (IL-6) inhibitor on streptozotocin-induced diabetic nephropathy. Male Sprague-Dawley rats (n = 36) were distributed into six groups and treated for 4 weeks. Groups 1, 3, 5 received either saline, tocilizumab (2 mg/kg), or tocilizumab (8 mg/kg) injection intraperitoneally (i.p.), every 2 weeks, respectively. Groups 2, 4, 6 were rendered diabetic by a single i.p. injection of streptozotocin (65 mg/kg) and were treated as in groups 1, 3, 5, respectively. Biochemical parameters were measured in plasma, urine, and kidneys. In the untreated diabetic group, there was a significant decrease in body weight, polyuria, and increased kidney weight. There was increased urinary albumin/creatinine ratio (UACR) and N-acetyl-β-D-glucosaminidase (NAG)/creatinine ratio (UNCR). Streptozotocin also induced a significant increase in creatinine clearance. In addition, diabetes was associated with increased oxidative stress [reduced renal glutathione reductase (GR), superoxide dismutase (SOD), catalase activities, and increased malondialdhyde (MDA)] and increased plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) concentrations. Kidneys from streptozotocin-treated rats showed marked vacuolation of the proximal tubular epithelium with focal tubular necrosis and the glomeruli showing increase in mesangial cells. Tocilizumab significantly mitigated the increase in UACR and UNCR, renal MDA, plasma TNF-α, IL-6 and NO levels, and the decrease in renal SOD and catalase activities in diabetic rats. Tocilizumab did not significantly improve creatinine clearance; however, it attenuated the histopathological changes induced by streptozotocin. This study shows that tocilizumab was able to ameliorate some of the changes seen in streptozotocin-induced early diabetic nephropathy in rats. This is mainly due to its anti-inflammatory and antioxidative effects.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Glutathione reductase
Anti-Inflammatory Agents
Renal function
Antibodies, Monoclonal, Humanized
Kidney
Antioxidants
Diabetes Mellitus, Experimental
Nephropathy
Rats, Sprague-Dawley
Diabetic nephropathy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Tocilizumab
Diabetes mellitus
Internal medicine
medicine
Animals
Hypoglycemic Agents
Diabetic Nephropathies
Pharmacology
Creatinine
Interleukin-6
business.industry
Body Weight
Organ Size
General Medicine
medicine.disease
Streptozotocin
Rats
Oxidative Stress
030104 developmental biology
Endocrinology
chemistry
030220 oncology & carcinogenesis
business
Injections, Intraperitoneal
medicine.drug
Subjects
Details
- ISSN :
- 14321912 and 00281298
- Volume :
- 392
- Database :
- OpenAIRE
- Journal :
- Naunyn-Schmiedeberg's Archives of Pharmacology
- Accession number :
- edsair.doi.dedup.....9a05e8134026591b0c132e7d851a435c