The effects of delta-9-tetrahydrocannabinol on Kruppel-like factor-4 expression, redox homeostasis, and inflammation in the kidney of diabetic rat

YANAR K. , Coskun Z. M. , Beydogan A. B. , AYDIN S. , Bolkent S.

JOURNAL OF CELLULAR BIOCHEMISTRY, cilt.120, ss.16219-16228, 2019 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 120 Konu: 9
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1002/jcb.28903
  • Sayfa Sayıları: ss.16219-16228


Diabetes mellitus is a complex, multifactorial disorder that is attributed to pancreatic beta cell dysfunction. Pancreatic beta cell dysfunction results in declining utilization of glucose by peripheral tissues as kidney and it leads to nephropathy. Excessive production and accumulation of free radicals and incapable antioxidant defense system lead to impaired redox status. Macromolecular damage may occur due to impaired redox status and also immune imbalance. Delta 9-Tetrahydrocannabinol (THC) is the main active ingredient in cannabis. THC acts as an immunomodulator and an antioxidant agent. Our aim was to evaluate the effects of THC in the diabetic kidney. We analyzed macromolecular damage biomarkers as protein carbonyl (PCO), lipid hydroperoxide (LHP), malondialdehyde (MDA), 8-hydroxy-2 '-deoxyguanosine (8-OHdG), and antioxidant defense system biomarkers as thiol fractions (T-SH, NP-SH, P-SH) and Cu/Zn-superoxide dismutase activity for the antioxidative effects of THC. Furthermore, mRNA expression of Kruppel-like factor-4, secreted immunopositive cell number changes of interleukin-6, nuclear factor kappa beta (NF-kappa beta), and peroxisome proliferator-activated receptor-gamma and tumor necrosis factor alpha (TNF-alpha) levels were analyzed for the immunomodulatory activity of THC. Diabetic rats showed significantly increased levels of PCO, LHP, MDA, and 8-OHdG when compared with controls (P < 0.05 for each parameter). THC significantly reduced the elevated levels of PCO and 8-OHdG (P < 0.05 for both parameters) and also LHP and MDA levels were insignificantly reduced by THC. Also, thiol fractions insignificantly increased in THC administered diabetic kidney when compared with diabetic rats. The NF-kappa beta cell number significantly decreased in the diabetic rats treated with THC compared with the diabetic group. According to our data, THC has ameliorative effects on the impaired redox status of diabetic kidney and also it acts as an immunomodulator. Therefore, THC might be used as a therapeutic agent for diabetic kidneys but its usage in the healthy kidney may show adverse effects.