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The transient receptor potential ankyrin 1 (TRPA1) channels, characterized as nonselective cation channels with permeability to calcium ions (Ca 2 + ), are part of the extensive family of transient receptor potential (TRP) channels. Research has demonstrated that TRPA1 channels function as sensors for oxidative stress in the renal tubules. Additionally, TRPA1 expression has increased in renal tissue following ischemia-reperfusion (IR). There is also a significant correlation between IR-induced renal injury and TRPA1 expression. This study investigated the effects of selective TRPA1 agonist ASP7663 and selective TRPA1 antagonist HC-030031 on renal IR injury. A total of 40 rats were divided into four groups: control, IR, IR+ASP7663, and IR + HC-030031. The rat kidneys were exposed to 45 min of ischemia, followed by 24 h of reperfusion. TRPA1 agonist ASP7663 and selective TRPA1 antagonist HC-030031 were administered intraperitoneally to the treatment groups with renal IR. HC-030031 administration reduced the elevated kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine (Cre) caused by renal IR. HC-030031 administration reduced the increased histopathological damage in renal tissue due to IR. It also reduced renal tissue interleukin-1beta (IL-1β), interleukin-6 (IL-6), toll-like receptor-4 (TLR-4), phosphorylated-NF-κB, phosphorylated-IκB-α, tumor necrosis factor-alpha (TNF-α), and caspase-3 levels. In this study, TRPA1 antagonist HC-030031 showed a protective behavior on renal IR injury by averting inflammation and apoptosis. After further studies, TRPA1 inhibition may be a new treatment strategy to prevent renal IR injury., (© 2025 Wiley Periodicals LLC.)

Kidney ischemia reperfusion (IR) injury is an important health problem resulting in acute renal failure. After IR, the inflammatory and apoptotic process is triggered. The relation of Cannabinoid type 2 (CB2) receptor with inflammatory and apoptotic process has been determined. The CB2 receptor has been shown to be localized in glomeruli and tubules in human and rat kidney. Activation of CB2 receptor with JWH-133 has been shown to reduce apoptosis and inflammation. In this study, it was investigated whether CB2 activation with selective CB2 receptor agonist JWH-133 was protective against renal IR injury. Male Sprague-Dawley rats were divided into 5 groups (n = 45). Bilateral ischemia was treated to the IR group rat's kidneys for 45 min and then reperfusion was performed for 24 h. Three different doses of JWH-133 (0.2, 1 and 5 mg/kg) were administered to the treatment groups at the onset of ischemia. The JWH-133 application at three different doses decreased the glomerular and tubular damage. Additionally, in the renal tissue, nuclear factor-κB, tumour necrosis factor alpha, interleukin-1beta, and caspase-3 levels decreased immunohistochemically. Similarly, JWH-133 application decreased the serum tumour necrosis factor alpha, blood urea nitrogen, creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, Cystatin C, interleukin-18, interleukin-1beta, interleukin-6, and interleukin-10 levels. We found that JWH-133 and CB2 receptor activation had a curative effect against kidney IR damage. JWH-133 may be a new therapeutic agent in preventing kidney IR damage.

Apelin is a peptide hormone defined as a ligand for G-protein clamped receptor (APJ) receptor. It is indicated in the literature both apelin and APJ are synthesized on the peripheral tissues including the renal tissues. Which roles does the apelin play on the renal tissue has not been completely illuminated yet. This study is designed to determine the possible protective effect of apelin-13 on the kidney I/R injury. Adult male Sprague-Dawley rats were used in this study. In the sham group, right kidneys of the animals were dissected. In the I/R group, right kidney was dissected and ischemia of 45 min was performed, and then reperfusion was applied for 3 h. In the treatment groups, three different doses of apelin were injected at the beginning of the ischemia unlike the I/R group. BUN, Cre, Na, K, Cl, total protein and albumin from serum samples were determined and TNF-α, IL-1β, IL-6, TAS and TOS parameters were read with ELISA reader. MDA, SOD, CAT and GSH-Px enzyme activations from renal tissues were measured. In comparison with the sham and I/R groups, while the serum BUN, CRE, CI and TNF-α levels showed an increase in the groups on which the apelin-13 was applied, Na, total protein, albumin, TAS levels decreased. Serum TOS level of other groups showed an increase by comparison with the sham group. Our results showed that apelin-13 applied after I/R increased the antioxidant enzyme activity in a dose dependent manner, prevented the lipid oxidation and improved the renal functions.

• The FAAH and MAGL enzymes that degrade AEA and 2-AG are expressed in the kidney. • Endocannabinoid substances AEA and 2-AG level are associated with IR damage. • Inhibition of FAAH and MAGL reduced inflammation caused by renal ischemia reperfusion injury. • FAAH and MAGL inhibition also reduced kidney dysfunction and apoptosis. Arachidonoyl ethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) are the most studies endocannabinoids. AEA and 2-AG are degraded by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes, respectively. FAAH and MAGL enzymes are widely expressed in many tissues, including kidney. Recent works have depicted that AEA and 2-AG levels are associated with ischemia–reperfusion (IR) injury. In this study, we investigated the effects of MAGL inhibitor KML29 and FAAH inhibitor URB597 against kidney IR injury. The kidneys of the rats underwent ischemia for 45 min and then reperfusion for 24 h. KML29 and URB597 were administered intraperitoneally with kidney IR to two different treatment groups. IR application increased serum blood urea nitrogen (BUN), creatinine (Cre), interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels, while these parameters were decreased following KML29 and URB597 administration. KML29 and URB597 administration also reduced the increased toll-like receptor-4 (TRL-4), phosphorylated-NF-κB, phosphorylated-IκB-α, tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), caspase-3 levels and histopathological damage in kidney tissue. Our results reveal that MAGL inhibitor KML29 and FAAH inhibitor URB597 have a protective effect on kidney IR injury by preventing apoptosis and inflammation. Inhibition of MAGL and FAAH may be a new therapeutic strategy to prevent kidney IR injury. [ABSTRACT FROM AUTHOR]

AIM: The endocannabinoid system is a physiological system that has been defined in the last 20-30 years. Anandamide and 2-arachidonoylglycerol (2-AG) have been identified as the most important endocannabinoid substances in the body. Anandamide is degraded by the fatty acid amide hydrolase (FAAH) enzyme, while 2-AG is degraded by the monoacylglycerol lipase (MAGL) enzyme. FAAH and MAGL enzymes are widely expressed in many tissues, including the kidney. Anandamide and 2-AG levels have been shown to be associated with ischemia-reperfusion (IR) injury. Although the protective properties of different FAAH and MAGL inhibitors against IR damage have been shown in various studies, the effect of MAGL inhibitor KML29 and FAAH inhibitor URB597 on kidney IR damage has not been investigated. In this study, we investigated the protective effect of MAGL inhibitor KML29 and FAAH inhibitor URB597 against kidney IR injury. METHODS: 60 Sprague Dawley male rats were randomly divided into 6 groups (1. control 2. IR 3. KML29 4. KML29+IR 5. URB597 6. URB597+IR). The kidneys of the rats were bilaterally administered 45 minutes of ischemia and 24 hours of reperfusion. KML29 and URB597 were administered intraperitoneally to the treatment groups at the onset of ischemia. At the end of the experiment, histopathological damage and immunohistochemically caspase-3, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) levels were measured in the kidney tissue. RESULTS: Histopathological damage, caspase-3, TNF-α, IL-1β and IL-6 levels in the kidney tissue were decreased in the groups treated with KML29 and URB597 compared to the IR group (P<0.05). CONCLUSION: In this study, we found the curative effect of MAGL and FAAH enzyme inhibitors KML29 and URB597 against kidney IR injury. [ABSTRACT FROM AUTHOR]