The musculoprotective effects of thymoquinone on ameliorating soleus muscle damage induced by valproic acid in rats

Year 2022, Volume: 8 Issue: 3, 170 - 180, 31.12.2022

Sebile Azirak Deniz Taştemir Korkmaz Sedat Bilgiç Murat Sevimli Mehmet Kaya Özer

https://doi.org/10.30569/adiyamansaglik.1202066

Abstract

Aim: To determine the potential musculoprotective effects of thymoquinone (TQ) on valproic acid (VPA)-induced muscle damage.

Materials and Methods: Twenty-one male Spraque-Dawley rats were randomly separated into 3 groups (n = 7): Control, VPA, VPA + TQ. Oral VPA (500 mg/kg/day) and TQ (50 mg/kg/day) were given to the rats for a period of 14 days. On the 15th day, soleus muscle tissues were taken for evaluating the expression levels of the Alpha-actinin-3 (ACTN3) and Myosin heavy chain 7 (MYH7) genes and histological analysis.

Results: The VPA + TQ group showed significantly higher ACTN3 and lower MYH7 gene expression, and decreased NADPH oxidase-4 (NOX4) and caspase-3 (CAS-3) levels than the VPA group. Also, histopathological changes were decreased in the VPA + TQ group in comparison with the VPA group.

Conclusion: VPA-induced soleus muscle damage was alleviated due to the antioxidant and antiapoptotic effects of TQ. TQ may be beneficial in treating soleus muscle damage caused by VPA.

Keywords

Thymoquinone, Valproic acid, Apoptosis, Toxicity, Soleus muscle damage

Supporting Institution

Projeye destek veren bir kurum bulunmamaktadır.

Project Number

-

Thanks

We would like to thank the staffs of the Adıyaman University Experimental Animal Production, Application and Research Center

Sıçanlarda valproik asidin neden olduğu soleus kas hasarını iyileştirmede timokinonun koruyucu etkileri

Abstract

Amaç: Çalışmada timokinonun (TQ) valproik asit (VPA) kaynaklı kas hasarı üzerindeki potansiyel koruyucu etkilerinin belirlenmesi amaçlanmıştır.

Gereç ve Yöntem: Yirmi bir erkek Spraque-Dawley sıçan rastgele 3 gruba ayrıldı (n = 7): Kontrol, VPA, VPA + TQ. Sıçanlara 14 gün süreyle oral VPA (500 mg/kg/gün) ve TQ (50 mg/kg/gün) verildi. Onbeşinci günde, Alfa-aktinin-3 (ACTN3) ve Miyozin ağır zincir 7 (MYH7) genlerinin ekspresyon düzeylerinin belirlenmesi ve histolojik analiz için soleus kas dokuları alındı.

Bulgular: VPA + TQ grubunda, VPA grubuna göre önemli ölçüde daha yüksek ACTN3 ve daha düşük MYH7 gen ekspresyonu ile düşük NADPH oksidaz-4 (NOX4) ve kaspaz-3 (CAS-3) seviyeleri gözlendi. Ayrıca VPA + TQ grubunda VPA grubuna göre histopatolojik değişikliklerin azaldığı da görüldü.

Sonuç: TQ'un antioksidan ve antiapoptotik etkileri nedeniyle VPA kaynaklı soleus kas hasarını hafiflettiği ve kas hasarını tedavi etmede faydalı olabileceği sonucuna varılmıştır.

Keywords

Timokinon, Valproik asit, Apoptoz, Toksisite, Soleus kas hasarı

Project Number

-

References

• Romoli M, Mazzocchetti P, D'Alonzo R, et al. Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences. Curr Neuropharmacol. 2019;17(10):926-946.
• Lheureux PE, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol(Phila). 2009;47(2):101-111.
• Nanau RM, Neuman MG. Adverse drug reactions induced by valproic acid. Clin Biochem. 2013;46(15):1323-1338.
• Cornago M, Garcia-Alberich C, Blasco-Angulo N, et al. Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe. Cell Death Dis. 2014; 5(10):e1435.
• Yiew KH, Chatterjee TK, Hui DY, Weintraub NL. Histone Deacetylases and Cardiometabolic Diseases. Arterioscler Thromb Vasc Biol. 2015;35(9):1914-1919.
• Falkenberg KJ, Johnstone RW. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 2014;13(9):673-691.
• Moresi V, Marroncelli N, Pigna E, et al. Histone Deacetylase 4 is crucial for proper skeletal muscle development and disease. Italian Journal of Anatomy and Embryology. 2015;120(1):150.
• Alamdari N, Aversa Z, Castillero E, Hasselgren PO. Acetylation and deacetylation--novel factors in muscle wasting. Metabolism. 2013;62(1): 1-11.
• Turkyilmaz IB, Sokmen BB, Yanardag R. Alpha-lipoic acid prevents brain injury in rats administered with valproic acid. J Biochem Mol Toxicol. 2020;34(11):e22580.
• Tu C, Allen A, Deng W, et al. Commonly used thiol-containing antioxidants reduce cardiac differentiation and alter gene expression ratios of sarcomeric isoforms. Exp Cell Res. 2018;370(1):150-159.
• Wells PG, McCallum GP, Chen CS, et al. Oxidative stress in developmental origins of disease: teratogenesis, neurodevelopmental deficits, and cancer. Toxicol Sci. 2009;108(1):4-18.
• Bimonte S, Albino V, Barbieri A, et al. Dissecting the roles of thymoquinone on the prevention and the treatment of hepatocellular carcinoma: an overview on the current state of knowledge. Infect Agent Cancer. 2019;14:10.
• Allen DL, Loh AS. Posttranscriptional mechanisms involving microRNA-27a and b contribute to fast-specific and glucocorticoid-mediated myostatin expression in skeletal muscle. Am J Physiol Cell Physiol. 2011;300(1):C124-137.
• Stead CA, Hesketh SJ, Bennett S, et al. Fractional Synthesis Rates of Individual Proteins in Rat Soleus and Plantaris Muscles. Proteomes. 2020;8(2):10.
• Chakkalakal JV, Kuang S, Buffelli M, Lichtman JW, Sanes JR. Mouse transgenic lines that selectively label Type I, Type IIA, and Types IIX+B skeletal muscle fibers. Genesis. 2012;50(1):50-58.
• Bajek S, Bobinac D, Bajek G, Vranić TS, Lah B, Dragojević DM. Muscle fiber type distribution in multifidus muscle in cases of lumbar disc herniation. Acta Med Okayama. 2000;54(6):235-241.
• Narkar VA, Fan W, Downes M, et al. Exercise and PGC-1α-independent synchronization of type I muscle metabolism and vasculature by ERRγ. Cell metabolism. 2011;13(3):283-293.
• Karlsson J. Metabolic adaptations to exercise: a review of potential beta-adrenoceptor antagonist effects. Am J Cardiol. 1985;55(10):48d-58d.
• Kawano F, Nimura K, Ishino S, Nakai N, Nakata K, Ohira Y. Differences in histone modifications between slow- and fast-twitch muscle of adult rats and following overload, denervation, or valproic acid administration. J Appl Physiol (1985). 2015;119(10):1042-1052.
• Ogura Y, Naito H, Kakigi R, et al. Different adaptations of alpha-actinin isoforms to exercise training in rat skeletal muscles. Acta Physiol (Oxf). 2009;196(3):341-349.
• Saunders CJ, September AV, Xenophontos SL, et al. No association of the ACTN3 gene R577X polymorphism with endurance performance in Ironman Triathlons. Ann Hum Genet. 2007;71(Pt 6):777-781.
• Vincent B, De Bock K, Ramaekers M, et al. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics. 2007;32(1): 58-63.
• Berman Y, North KN. A gene for speed: The emerging role of α-actinin-3 in muscle metabolism. Physiology. 2010;25(4):250-259.
• Geng Z, Fan WY, Zhou B, et al. FNDC5 attenuates obesity-induced cardiac hypertrophy by inactivating JAK2/STAT3-associated inflammation and oxidative stress. J Transl Med. 2019;17(1):107.
• Jandreski MA, Sole MJ, Liew CC. Two different forms of beta myosin heavy chain are expressed in human striated muscle. Hum Genet. 1987;77(2):127-131.
• Honda M, Tsuchimochi H, Hitachi K, Ohno S. Transcriptional cofactor Vgll2 is required for functional adaptations of skeletal muscle induced by chronic overload. J Cell Physiol. 2019;234(5):15809-15824.
• Aires CC, van Cruchten A, Ijlst L, et al. New insights on the mechanisms of valproate-induced hyperammonemia: inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA. J Hepatol. 2011;55(2):426-434.
• Samarghandian S, Farkhondeh T, Samini F. A Review on Possible Therapeutic Effect of Nigella sativa and Thymoquinone in Neurodegenerative Diseases. CNS Neurol Disord Drug Targets. 2018;17(6):412-420.
• Zhu N, Xiang Y, Zhao X, et al. Thymoquinone suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation, migration and neointimal formation. J Cell Mol Med. 2019;23(12):8482-8492.
• Hosseinzadeh H, Taiari S, Nassiri-Asl M. Effect of thymoquinone, a constituent of Nigella sativa L., on ischemia-reperfusion in rat skeletal muscle. Naunyn Schmiedebergs Arch Pharmacol. 2012;385(5):503-508.
• Barrett CE, Hennessey TM, Gordon KM, et al. Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally. Mol Autism. 2017;8:42.
• Oztopuz O, Turkon H, Buyuk B, et al. Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats. Mol Biol Rep. 2020;47(1):317-325.
• Atta MS, Almadaly EA, El-Far AH, et al. Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression. Int J Mol Sci. 2017;18(5):919.
• Savran M, Ascı H, Armagan İ, et al. Thymoquinone could be protective against valproic acid-induced testicular toxicity by antioxidant and anti-inflammatory mechanisms. Andrologia. 2020;52(7):e13623.
• Star K, Edwards IR, Choonara I. Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. PLoS One. 2014;9(10):e108970.
• Wadzinski J, Franks R, Roane D, Bayard M. Valproate-associated hyperammonemic encephalopathy. J Am Board Fam Med. 2007;20(5):499-502.
• Azırak S, Bilgiç S, Taştemir Korkmaz D, Sevimli M, Özer MK. Effect of thymoquinone on ameliorating valproic acid-induced damage in pancreatic tissue of rats. Cukurova Med J. 2022;47(1):350-359.
• Nakamura K, Yamane K, Shinohara K, et al. Hyperammonemia in idiopathic epileptic seizure. Am J Emerg Med. 2013;31(10):1486-1489.
• Yang N, Garton F, North K. Alpha-actinin-3 and performance. Med Sport Sci. 2009;54:88-101.
• MacArthur DG, Seto JT, Raftery JM, et al. Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet. 2007;39(10):1261-1265.
• Del Coso J, Valero M, Salinero JJ, et al. ACTN3 genotype influences exercise-induced muscle damage during a marathon competition. Eur J Appl Physiol. 2017;117(3):409-416.
• Tassinari V, De Gennaro V. Atrophy, oxidative switching and ultrastructural defects in skeletal muscle of the ataxia telangiectasia mouse model. J Cell Sci. 2019;132(5):jcs223008.
• Lowes BD, Minobe W, Abraham WT, et al. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest. 1997;100(9):2315-2324.
• Marian AJ, Braunwald E. Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy. Circ Res. 2017;121(7):749-770.
• Oldfors A, Lamont PJ. Thick filament diseases. Adv Exp Med Biol. 2008;642:78-91.
• Ko JY, Lee M, Jang JH, Jang DH, Ryu JS. A novel de novo mutation in MYH7 gene in a patient with early onset muscular weakness and severe kyphoscoliosis: A case report. Medicine (Baltimore). 2019;98(28):e16389.
• Hou N, Mai Y, Qiu X, et al. Carvacrol Attenuates Diabetic Cardiomyopathy by Modulating the PI3K/AKT/GLUT4 Pathway in Diabetic Mice. Front Pharmacol. 2019;10:998.
• Abd Al Haleem EN, Hasan WYS, Arafa HMM. Therapeutic effects of thymoquinone or capsaicin on acrylamide-induced reproductive toxicity in rats mediated by their effect on oxidative stress, inflammation, and tight junction integrity. Drug Chem Toxicol. 2022;45(5):2328-2340.
• Gholamnezhad Z, Havakhah S, Boskabady MH. Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol. 2016;190:372-386.
• Gallo BV, Slater JD, Toledo C, DeToledo J, Ramsay RE. Pharmacokinetics and muscle histopathology of intramuscular valproate. Epilepsy Res. 1997;28(1):11-15.
• Hagiwara H, Saito F, Masaki T, et al. Histone deacetylase inhibitor trichostatin A enhances myogenesis by coordinating muscle regulatory factors and myogenic repressors. Biochem Biophys Res Commun. 2011;414(4):826-831.
• Dash SK, Chattopadhyay S, Ghosh T, et al. Self-assembled betulinic acid protects doxorubicin induced apoptosis followed by reduction of ROS-TNF-α-caspase-3 activity. Biomed Pharmacother. 2015;72:144-157.
• Taştemir Korkmaz D, Azırak S, Bilgiç S, Bayram D, Özer MK. Thymoquinone reduced RIPK1-dependent apoptosis caused by valproic acid in rat brain. Ann Med Res. 2021;28(11):2005-11
• Kaarniranta K, Pawlowska E, Szczepanska J, Jablkowska A. Role of Mitochondrial DNA Damage in ROS-Mediated Pathogenesis of Age-Related Macular Degeneration (AMD). Int J Mol Sci. 2019;20(10):2374.
• Ishii T, Sekiguchi M. Two ways of escaping from oxidative RNA damage: Selective degradation and cell death. DNA Repair (Amst). 2019;81:102666.
• He LL, Wu XX, Wang YX, et al. Spectroscopic investigation on the sonodynamic damage to protein in the presence of eosine B. Ultrason Sonochem. 2015;26:93-98.
• Han W, Yu F, Wang R, Guan W. Valproic Acid Sensitizes Glioma Cells to Luteolin Through Induction of Apoptosis and Autophagy via Akt Signaling. Cell Mol Neurobiol. 2021;41(8):1625-1634.
• Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD, Sadoshima J. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci U S A. 2010;107(35):15565-15570.
• Lin J, Fang L, Li H, et al. Astragaloside IV alleviates doxorubicin induced cardiomyopathy by inhibiting NADPH oxidase derived oxidative stress. Eur J Pharmacol. 2019;859:172490.
• Al-Majed AA, Daba MH, Asiri YA, Al-Shabanah OA, Mostafa AA, El-Kashef HA. Thymoquinone-induced relaxation of guinea-pig isolated trachea. Res Commun Mol Pathol Pharmacol. 2001;110(5-6):333-345.