Δ(9)-tetrahydrocannabinol protects cardiac tissue against endoplasmic reticulum and oxidative stresses, apoptosis, and inflammation in rats with hyperinsulinemia


Yazici Z. M. C., YANAR K., BOLKENT H. S.

JOURNAL OF PHARMACY AND PHARMACOLOGY, cilt.76, sa.6, ss.701-709, 2024 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 76 Sayı: 6
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1093/jpp/rgae023
  • Dergi Adı: JOURNAL OF PHARMACY AND PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, Veterinary Science Database
  • Sayfa Sayıları: ss.701-709
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Objectives: In our study, we aimed to examine how delta(9)-tetrahydrocannabinol (THC) administration to hyperinsulinemia (HI) model rats would change endoplasmic reticulum stress (ERS), apoptosis, inflammation, and oxidative stress in cardiac tissue. Methods: Rats were divided into four groups (n = 32): Control (C), THC, HI, and Treatment (Tre). Fructose (10%) in the drinking water was given to HI and Tre rats for 12 weeks. 1.5 mg/kg/d THC was given intraperitoneally to THC and Tre rats in the last 4 weeks of the experiment. The mRNA expressions of ERS and apoptosis markers in the cardiac tissue were detected. TNF-alpha concentration and oxidative stress were also analyzed. Key findings: THC treatment in rats with HI ameliorated the overexpression of GRP-78, IRE1 alpha, ATF6, ATF4, CHOP, Cas-12, Cas-8, Cas-9, and Cas-3 mRNAs, markers of ERS and apoptosis (P < .0001 for all). In addition, THC has been shown to reduce inflammation in the Tre group by causing a decrease in increased cardiac TNF-alpha levels (P < .01). Moreover, THC prevented cardiac tissue damage by regulating the degraded oxidative stress marker levels and antioxidant enzyme activities in HI. Conclusions: Our findings suggest that THC treatment in rats with HI exhibited a significant effect in ameliorating cardiac tissue damage by improving the antioxidant defense system, inflammation, apoptosis, ERS, and oxidative stress.