Thymoquinone protects the rat kidneys against renal fibrosis

Rahimeh Bargi, Fereshteh Asgharzadeh, Farimah Beheshti, Mahmoud Hosseini, Mehdi Farzadnia, Majid Khazaei

Abstract


Thymoquinone (TQ) is the main active ingredient of Nigella sativa seeds with various pharmacological effects. The aim of this study was to investigate the effect of TQ on renal fibrosis and permeability and oxidative stress status in lipopolysaccharide (LPS)-induced inflammation in male rats. Eighty male Wistar rats were divided into 5 groups as follow: control (received normal saline), LPS (1 mg/kg/day), and LPS+TQ (by doses of 2, 5 and 10 mg/kg/day). After three weeks, the biochemical parameters such as blood urea nitrogen (BUN) and creatinine in serum samples, oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase (CAT) activities in renal tissue homogenate and renal permeability (evaluated by Evan's blue dye method) were measured and renal fibrosis was evaluated, histologically using Masson's trichrome staining. LPS administration induced renal fibrosis (1.49 ± 0.08 vs. 7.15 ± 0.18%) and significantly increased renal permeability (6.03 ± 1.05 vs. 13.5 ± 1.04 µg evans blue(EB)/g tissue), serum BUN and creatinine levels and oxidative stress marker (MDA) (P < 0.05), while, it reduced anti-oxidative markers including total thiol group, SOD and CAT activities (P < 0.05). Administration of TQ significantly improved these alterations which were dose-dependent in oxidative stress markers, renal permeability (TQ 2, 5 and 10 mg/kg: 10.7 ± 0.3, 9.2 ± 1.4 and 11.5 ± 0.6 µg EB/g tissue; respectively) and fibrosis (TQ 2, 5 and 10 mg/kg: 6.09 ± 0.7, 4.26 ± 0.14 and 2.52 ± 0.08%; respectively). In conclusion, administration of TQ reduced renal fibrosis and permeability and improved oxidative stress status. Thus, TQ can be considered in conditions accompanied with chronic inflammation at least as a part of treatment strategy.


Keywords


Thymoquinone; Lipopolysaccharide; Renal; Fibrosis; Permeability

Full Text:

PDF

References


Lawson J, Elliott J, Wheeler-Jones C, Syme H, Jepson R. Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury. Vet J. 2015;203(1):18-26.

Liu Y. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int. 2006;69(2):213-217.

Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002;71:635-700.

Bhattacharyya J, Biswas S, Datta AG. Mode of action of endotoxin: role of free radicals and antioxidants. Curr Med Chem. 2004;11(3):359-368.

Helmersson J, Vessby B, Larsson A, Basu S. Association of type 2 diabetes with cyclooxygenase-mediated inflammation and oxidative stress in an elderly population. Circulation. 2004;109(14):1729-1734.

Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012;83(4):443-451.

Ragheb A, Attia A, Eldin WS, Elbarbry F, Gazarin S, Shoker A. The protective effect of thymoquinone, an anti-oxidant and anti-inflammatory agent, against renal injury: a review. Saudi J Kidney Dis Transpl. 2009;20(5):741-752.

Bargi R, Asgharzadeh F, Beheshti F, Hosseini M, Sadeghnia HR, Khazaei M. The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats. Cytokine. 2017;96:173-184.

Khazaei M, Nematbakhsh M. Coronary vascular and aortic endothelial permeability during estrogen therapy: a study in DOCA-salt hypertensive ovariectomized rats. Physiol Res. 2004;53(6):609-614.

Ko YH, Tsai MS, Lee PH, Liang JT, Chang KC. Methylprednisolone stiffens aortas in lipopolysaccharide-induced chronic inflammation in rats. PloS one. 2013;8(7):e69636.

Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med. 1990;9(6):515-540.

Sadeghnia HR, Kamkar M, Assadpour E, Boroushaki MT, Ghorbani A. Protective Effect of Safranal, a Constituent of Crocus sativus, on Quinolinic Acid-induced Oxidative Damage in Rat Hippocampus: Iran J Basic Med Sci. 2013;16(1):73-82.

Madesh M, Balasubramanian KA. Microtiter plate assay for superoxide dismutase using MTT reduction by superoxide. Indian J Biochem Biophys. 1998;35(3):184-188.

Aebi HE. Catalase. In: HU B, editor. Methods in Enzymatic Analysis. New York: Academic Press; 1983. pp. 276-286.

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676-682.

Burits M, Bucar F. Antioxidant activity of Nigella sativa essential oil. Phytother Res. 2000;14(5):323-328.

Rodríguez-Iturbe B, García García G. The role of tubulointerstitial inflammation in the progression of chronic renal failure. Nephron Clin Pract. 2010;116(2):c81-c8.

Asgharzadeh F, Rouzbahani R, Khazaei M. Chronic low-grade inflammation: Etiology and its effects. J Isfahan Med. 2016;34(379):408-421.

Norouzi F, Abareshi A, Asgharzadeh F, Beheshti F, Hosseini M, Farzadnia M, et al. The effect of Nigella sativa on inflammation-induced myocardial fibrosis in male rats. Res Pharm Sci. 2017;12(1):74-81.

Kheir-Eldin AA, Motawi TK, Gad MZ, Abd-ElGawad HM. Protective effect of vitamin E, β-carotene and N-acetylcysteine from the brain oxidative stress induced in rats by lipopolysaccharide. Int J Biochem Cell Biol. 2001;33(5):475-482.

Kacem M, Simon G, Leschiera R, Misery L, ElFeki A, Lebonvallet N. Antioxidant and anti-inflammatory effects of Ruta chalepensis L. extracts on LPS-stimulated RAW 264.7 cells. In Vitro Cell Devl Biol-Anim. 2015;51(2):128-141.

Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact. 2012;197(1): 40-46.

Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013;3(5):337-352.

Sayed‐Ahmed MM, Nagi MN. Thymoquinone supplementation prevents the development of gentamicin‐induced acute renal toxicity in rats. ClinExp Pharmacol Physiol. 2007;34(5‐6): 399-405.

Ulu R, Dogukan A, Tuzcu M, Gencoglu H, Ulas M, İlhan N, et al. Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury. Food chem Toxicol. 2012;50(5):1675-1659.

Liu D, Zhang D, Scafidi J, Wu X, Cramer CC, Davis AE. C1 inhibitor prevents Gram-negative bacterial lipopolysaccharide-induced vascular permeability. Blood. 2005;105(6):2350-2355.

Vanhoutte PM, Shimokawa H, Tang EH, Feletou M. Endothelial dysfunction and vascular disease. Acta Physiol. 2009;196(2):193-222.

Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 2013;12(1):86.

Strutz F, Zeisberg M. Renal fibroblasts and myofibroblasts in chronic kidney disease. J Am Soc Nephrol. 2006;17(11):2992-2998.

Pulskens WP, Rampanelli E, Teske GJ, Butter LM, Claessen N, Luirink IK, et al. TLR4 promotes fibrosis but attenuates tubular damage in progressive renal injury. J AmSoc Nephrol. 2010;21(8):1299-1308.

El-Khouly D, El-Bakly WM, Awad AS, El-Mesallamy HO, El-Demerdash E. Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats. Toxicology. 2012;302(2):106-113.

Oguz S, Kanter M, Erboga M, Erenoglu C. Protective effects of thymoquinone against cholestatic oxidative stress and hepatic damage after biliary obstruction in rats. J Mol Histol. 2012;43(2):151-159.


Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.