Abstract: TH-PO080
Cannabigerolic Acid (CBGA) Ameliorates Renal Inflammation and Fibrosis in Mouse Nephropathic Models
Session Information
- AKI: Mechanisms - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Suzuki, Sayuri, The Queen's Medical Center, Honolulu, Hawaii, United States
- Fleig, Andrea, The Queen's Medical Center, Honolulu, Hawaii, United States
- Penner, Reinhold, The Queen's Medical Center, Honolulu, Hawaii, United States
Group or Team Name
- Queen's Center for Biomedical Research.
Background
Cannabinoids are a major class of compounds in cannabis, comprising some ~100 structurally related but diverse molecules, where cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA) being the major components in most plant varieties. In some plant varieties, cannabigerolic acid (CBGA) has been reported the dominant molecular species. CBD, the decarboxylated version of CBDA, is thought have multiple biological effects, including the ability to attenuate inflammatory processes. Cannabigerols (CBGA and its decarboxylated CBG molecule) have pharmacological profiles similar to CBD. The endocannabinoid system has recently emerged to contribute to kidney disease, however, the therapeutic property of cannabinoids in kidney disease remains largely unknown. In this study, we determined whether CBD and CBGA can attenuate kidney damage in cisplatin-induced acute kidney injury model. In addition, we evaluated the anti-fibrosis effect of these cannabinoids in Unilateral Ureteral Obstruction (UUO) mice as a chronic kidney disease model.
Methods
CBD or CBGA (10 mg/kg) were injected daily in cisplatin administered mice and UUO mice. Kidneys were collected at day 3 from cisplatin administered mice and used for qRT-PCR, western blotting and TUNEL assay. UUO Kidneys were collected at day 7 and used for immunostaining of Ki-67 and extracellular matrix. We also assessed the effect of CBGA and CBD to ion channel by patch-clamp technique.
Results
We find that CBGA protects the kidney from cisplatin-induced nephrotoxicity. CBGA also strongly suppressed mRNA of inflammatory cytokines and apoptosis through inhibition of caspase-3 activity in cisplatin-induced acute kidney injury, whereas CBD treatment was only partially effective. In UUO kidneys, both CBGA and CBD prevented kidney atrophy, tubule loss, proliferation and maintained overall morphology. Both cannabinoids also strongly reduced renal fibrosis in UUO kidneys. Finally, we find that in contrast to CBD, CBGA has a potent inhibitory effect on the channel-kinase TRPM7 and the TRPM7 protein expression was significantly suppressed in cisplatin-induced acute kidney injury.
Conclusion
We conclude that CBGA and CBD have a reno-protective efficacy in kidney damage, with CBGA especially having a stronger inhibitory effect to prevent inflammation in acute kidney injury by TRPM7 blockage.
Funding
- Other NIH Support