Therapeutic Effect of D-Carvone on Inflammation, Apoptosis, and Cell Damage in Lithium-Induced Liver Injury Model in Rats

Year 2024, , 95 - 101, 25.10.2024

Elif Erbaş , Volkan Gelen , Emre Öztürk

https://doi.org/10.47748/tjvr.1428357

Abstract

Objective: Lithium is an element denoted by the symbol Li in the periodic table. Lithium salts are widely used worldwide as therapeutic agents in the treatment of excitement. However, the use of lithium causes liver damage. Carvone is an unsaturated monoterpenoid ketone usually found in essential oil extracts of aromatic medicinal plants such as dill, mint, and cumin. Various studies have shown that D-Carvone has strong antioxidant and anti-inflammatory effects. In this study, it was aimed to investigate the protective effect of D-carvone on apoptosis, inflammation, and cell damage in lithium-induced liver injury.
Materials and Methods: The rats in our study were divided into 4 groups control, D-Carvone, Lithium and Lithium+D-Carvone. After the treatments, rats were decapitated and liver tissues were removed.
Results: We determined that lithium administration caused liver tissue damage and increased Bax, P2X7R, and Nfkβ-p65 expression and decreased Bcl-2 expression. D-Carvone administration prevented these changes.
Conclusion: As a result, it was observed that D-Carvone administration prevented lithium-induced liver tissue damage and showed this effect by suppressing the inflammatory and apoptotic process.

Keywords

Lithium, D-Carvone, Bax, P2X7R, Bcl-2, Nfkβ-p65

References

• Abbas BW, Kathem SH. Carvone attenuates irinotecan-induced intestinal mucositis and diarrhea in mice. Iraqi J Pharm Sci. 2021; 30(2):58-63.
• Abbas MM, Kandil Yİ, Abbas MA. R-(-)-carvone attenuated doxorubicin induced cardiotoxicity in vivo and potentiated its anticancer toxicity in vitro. Balkan Med J. 2020; 37(2):98-103.
• Alsanea S, Liu D. BITC and S-carvone restrain high-fat diet-induced obesity and ameliorate hepatic steatosis and insulin resistance. Pharm Res. 2017; 34(11):2241-2249.
• Alural B, Ozerdem A, Allmer J, Genc K, Genc S. Lithium protects against paraquat neurotoxicity by NRF2 activation and miR-34a inhibition in SH-SY5Y cells. Front Cell Neurosci. 2015; 28(9):209.
• Aniya Y, Matsusaki K. Effects of neutral salts on hepatic microsomal drug-metabolizing enzyme system in rats. Jpn J Pharmacol. 1983; 33(3):647-653.
• Arguin G, Bourzac JF, Placet M, et al. The loss of P2X7 receptor expression leads to increase intestinal glucose transit and hepatic steatosis. Sci Rep. 2017; 7:1-16.
• Ben Saad A, Dalel B, Rjeibi I, et al. Phytochemical, antioxidant and protective effect of cactus cladodes extract against lithium-induced liver injury in rats. Pharm Biol. 2017; Dec;55(1):516-525.
• Bouyahya A, Mechchate H, Benali T, Ghchime R, Charfi S, Balahbib A. Health benefits and pharmacological properties of carvone. Biomolecules. 2021; 11(12):1-26.
• Casado M, Aragon MC, Gimémez C. Determination of monoamines in rat brain regions after chronic administration of lithium. Neurochem Res, 1989; 14: 905-908.
• Dai M, Wu L, Yu K, et al. D-Carvone inhibit cerebral ischemia/reperfusion induced inflammatory response TLR4/NLRP3 signaling pathway. Biomed Pharmacother. 2020; 132:110870.
• Das S, Seth RK, Kumar A, et al. Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis. Am J Physiol Liver Physiol. 2013; 305:950-963.
• Engin AB, Engin A, Engin ED, Memis L. Does lithium attenuate the liver damage due to oxidative stress and liver glycogen depletion in experimental common bile duct obstruction? Toxicol Appl Pharmacol. 2023; 466:116489.
• Erbaş E, Gelen V, Kara H, et al. Silver nanoparticles loaded with oleuropein reduce doxorubicin-induced testicular damage by regulating endoplasmic reticulum stress, and apoptosis. Biol Trace Elem Res. 2024; 10:1-12.
• Gelen V, Özkanlar S, Kara A, Yeşildağ A. Citrate-coated silver nanoparticles loaded with agomelatine provide neuronal therapy in acute cerebral ischemia/reperfusion of rats by inhibiting the oxidative stress, endoplasmic reticulum stress, and P2X7 receptor-mediated inflammasome. Environ Toxicol. 2024; 39(3):1531-1543.
• Ghoshdastidar D, Poddar MK. Long term effect of lithium on brain regional catecholamine metabolism. Indian J Exp Biol, 1990; 28(5): 444-450.
• Gopalakrishnan T, Ganapathy S, Veeran V, Namasivayam N. Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events. Biomed Pharmacother. 2019; 111:178-187.
• Günther J, Schneider I, Krämer A. Carvone prevents and alleviates hepatic steatosis in rat model with nonalcoholic fatty liver disease. GMJ Med. 2019; 3(1):118–24.
• Hoque R, Sohail MA, Salhanick S. P2X7 receptormediated purinergic signaling promotes liver injury in acetaminophen hepatotoxicity in mice. Am J Physiol- Gastrointest Liver Physiol. 2012; 302(10):1171-1179.
• Huang C, Yu W, Cui H. P2X7 blockade attenuates mouse liver fibrosis. Mol Med Rep. 2014; 9:57-62.
• Hunt GE, Beilharz GR, Storlien LH, Kuchel PW, Johnson GF. The effect of lithium on rat erythrocyte choline, glycine and glutathione levels. Biochemical Pharmacol. 1983; 32(19):2981-2983.
• Johnson G, Gershon S. Early North American Research on Lithium. Aust N Z J Psychiatry. 1999; 33:48-53.
• Kara A, Ozkanlar S. Blockade of P2X7 receptor-mediated purinergic signaling with A438079 protects against LPS-induced liver injury in rats. J Biochem Mol Toxicol. 2023; 37(10):23443.
• Laakso ML, Oja SS. Transport of tryptophan and tyrosine in rat brain slices in the presence of lithium. Neurochem Res, 1979; 4, 411-423.
• Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017; 2:1-9.
• Lv L, Yang N, Cao Y, Dang J, Cheng L, El-Sheikh MA. D-carvone inhibits the JAK/STAT3 signaling pathway and induced the apoptotic cell death in the human gastric cancer AGS cells. J Biochem Mol Toxicol. 2021; 35(5):1-7.
• Lydiard RB, Gelenberg A. Hazards and adverse effects oflithium. Ann Rev Med. 1982; 33:327-344.
• Mahboubi M. Caraway as important medicinal plants in management of diseases. Nat Products Bioprospect 2019; 9(1):1-11.
• Makola RT, Kgaladi J, More GK, Jansen van Vuren P, Paweska JT, Matsebatlela TM. Lithium inhibits NF-κB nuclear translocation and modulate inflammation profiles in Rift valley fever virus-infected Raw 264.7 macrophages. Virol J. 2021; 18(1):116.
• Mezni A, Khazri O, Jarnier F, et al. Hepatoprotective effect of grape seed and skin extract against lithium exposure examined by the window of proteomics. Dose Response. 2022; 20(4):15593258221141585.
• Mohamed ME, Younis NS. Ameliorative effect of D-Carvone against hepatic ischemia-reperfusion-induced injury in rats. Life (Basel). 2022; 12(10):1502
• Neamatallah T, El-Shitany NA, Abbas AT, Ali SS, Eid BG. Honey protects against cisplatin-induced hepatic and renal toxicity through inhibition of NF-κB-mediated COX-2 expression and the oxidative stress dependent BAX/Bcl-2/caspase-3 apoptotic pathway. Food & Function. 2018; 9:3743-3754.
• Niazvand F, Ashtari A, Chamkouri N, Azari M. Hepatoprotective effects of Alpinia officinarum rhizome extract on cisplatin-induced hepatotoxicity in rats: A biochemical, histopathological and immunohistochemical study. J Trace Elem Med Biol. 2023; 80:127306.
• Ogaly HA, Aldulmani SAA, Al-Zahrani FAM, Abd-Elsalam RM. D-Carvone attenuates CCl4-induced liver fibrosis in rats by inhibiting oxidative stress and TGF-ß 1/SMAD3 signaling pathway. Biology. 2022; 11:739.
• Pert A, Rosenblatt JE, Sivit C, Pert CB, Bunney Jr, WE. Long-term treatment with lithium prevents the development of dopamine receptor supersensitivity. Science. 1978; 201(4351): 171-173.
• Rhee C, Dantes R, Epstein L. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014. JAMA. 2017; 318:1241-1249.
• Rosenthal NE, Goodwin FK. The role of the lithium ion in medicine. Ann Rev Med. 1982; 33(1):555-568.
• Schou M, Amdiesen A, Eskajaer-Olsen T, Jemson SQ. Occur-rence of goiter during lithium treatment. Br J Med. 1968; 3:710-703.
• Sousa C, Neves BM, Leitão AJ, Mendes AF. Molecular mechanisms underlying the anti-inflammatory properties of (R)-(-)-Carvone: Potential Roles of JNK1, Nrf2 and NF-κB. Pharmaceutics. 2023; 5(1):249.
• Tandon A, Nagpaul JP, Dhawan D. Effect of lithium on thehepatic drug metabolizing enzymes of protein deficient rats. Biol Trace Elem Res. 1997; 59:1-7.
• Tondo L, Baldessarini RJ. Long-term Lithium Treatment in the Prevention of Suicidal Behavior in Bipolar Disorder Patients. Epidemiol Psichiatr Soc. 2009; 18:179-183.
• Zhao M, Du J. Anti-inflammatory and protective effects of d-carvone on lipopolysaccharide (LPS)-induced acute lung injury in mice. J King Saud Univ Sci. 2020; 32(2):1592-1596.
• Zhu X, Wang G, Wu S, Li C. Protective effect of D-Carvone against dextran sulfate sodium induced ulcerative colitis in Balb/c mice and LPS induced RAW cells via the inhibition of COX-2 and TNF-α. J Environ Pathol Toxicol Oncol. 2020; 39(3):235-245.