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Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-exposed Rats

Year 2025, Volume: 8 Issue: 5, 182 - 189, 15.09.2025

Dilek Kuzay

https://doi.org/10.19127/bshealthscience.1698368

Abstract

Mercury (Hg) is widely used in nature. It is a substance that has toxic effects even in small amounts. Thymoquinone (TQ) is the main active phenolic compound obtained from the essential oil of Nigella sativa L. (black cumin) seed. The protective effects of TQ against diseases and toxic compounds have been studied for a long time. Aim: This study aimed to investigate the effect of TQ on oxidative stress and behavior in rats exposed to mercury. In this study, 24 adult male Wistar Albino rats weighing between 250±20 g were used. 5 mg/kg Hg and 10 mg/kg TQ were given via intragastric gavage for 21 days. Animals were randomly divided into four groups. Group 1 is the Control, Group 2 TQ (10 mg/kg), Group 3 Hg (5 mg/kg), Group 4 Hg (5 mg/kg) + TQ (10 mg/kg). Open field test and forced swimming test were performed to examine locomotor activity, anxiety, and depression-like behaviors in rats. At the end of the experiment, Malondialdehyde (MDA), total nitric oxide (NO), and reduced glutathione (GSH/RSH) levels were examined in cerebral cortex and plasma. In the open field test, Hg+TQ treatment increased the number of crossings and time spent in the center (P<0.01). In the forced swim test, Hg+TQ treatment increased the swimming and climbing time (respectively P<0.01, P<0.001) and decreased the immobility time (P=0.001). In cerebral cortex and plasma, TQ treatment decreased the increased MDA and NO levels (p=0.01) and increased the decreased GSH/RSH levels (P<0.01) as a result of Hg exposure. Mercury exposure increased oxidative stress in plasma and cerebral cortex, causing anxiety and depression-like behaviors. TQ is can be used to improve some behavioral changes and reduce oxidative stress in Hg-exposed rats.

Keywords

Mercury Behavior Oxidative stress Nigella sativa Rats Antioxidants

Ethical Statement

The experimental procedures were approved by the Local Animal Care and Ethics Committee of Kırşehir Ahi Evran University, (approval date: March 18, 2024, protocol code: 68429034/04).

Project Number

This study was supported by Institutional Scientific Research Projects. The Project number is TIP.A3.24.011.

Thanks

This study was supported by Institutional Scientific Research Projects. The Project number is TIP.A3.24.011.

References

  • Abu-Elfotuh K, Abdel-Sattar SA, Abbas AN, Mahran YF, Alshanwani AR, Hamdan AME, Atwa AM, Reda E, Ahmed YM, Zaghlool SS, El-Din MN. 2023. The protective effect of thymoquinone or/and thymol against monosodium glutamate-induced attention-deficit/hyperactivity disorder (ADHD)-like behavior in rats: Modulation of Nrf2/HO-1, TLR4/NF-κB/NLRP3/caspase-1 and Wnt/β-catenin signaling pathways in rat model. Biomed Pharmacother, 162: 114735. https://doi.org/10.1016/j.biopha.2023.114735
  • Akarsu GD, Çetin A. 2022. The effect of thymoquinone on oxidative stress parameters and apolipoprotein E in Alzheimer model in rats. Dement Geriatr Cogn Disord, 51(4): 297-309. https://doi.org/10.1159/000522644
  • Aquib M, Najmi AK, Akhtar M. 2015. Antidepressant effect of thymoquinone in animal models of depression. Drug Res (Stuttg), 65(9):490-494. https://doi.org/10.1055/s-0034-1395621
  • Aykaç G, Uysal M, Yalçın AS, Koçak-Toker N, Sivas A, Oz H. 1985. The effects of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicol, 36: 71-76. https://doi.org/10.1016/0300-483X(85)90128-1
  • Barber SC, Shaw PJ. 2010. Oxidative stress in ALS: Key role in motor neuron injury and therapeutic target. Free Radic Biol Med, 48: 629-641. https://doi.org/10.1016/j.freeradbiomed.2009.11.018
  • Brocardo PS, Boehme F, Patten A, Cox A, Gil-Mohapel J, Christie BR. 2012. Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: Protective effects of voluntary physical exercise. Neuropharmacology, 62: 1607-1618. https://doi.org/10.1016/j.neuropharm.2011.10.006
  • Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. 1986. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol, 123: 520-531.
  • Firdaus F, Zafeer MF, Ahmad M, Afzal M. 2018. Anxiolytic and anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats. Heliyon, 4(6): e00650. https://doi.org/10.1016/j.heliyon.2018.e00650
  • Fouda AM, Daba MY, Dahab GM, Sharaf el-Din OA. 2008. Thymoquinone ameliorates renal oxidative damage and proliferative response induced by mercuric chloride in rats. Basic Clin Pharmacol Toxicol, 103(2): 109-118. https://doi.org/10.1111/j.1742-7843.2008.00267.x
  • Gstraunthaler G, Pfaller W, Kotanko P. 1983. Glutathione depletion and in vitro lipid peroxidation in mercury- or maleate-induced acute renal failure. Biochem Pharmacol, 32: 2969-2972. https://doi.org/10.1016/0006-2952(83)90513-4
  • Kurtel H, Granger DM, Tso P, Grisham MB. 1992. Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Physiol, 263(4 Pt 1): G573-G578. https://doi.org/10.1152/ajpgi.1992.263.4.G573
  • Kustimur S, Kalkanci A, Akbulut G, Gonul B, Bulduk E, Aksakal FN, Yetkin I. 2007. The effect of vaginal candidiasis on the levels of oxidative biomarkers in plasma and tissue samples of diabetic rats. Mycopathologia, 164(5): 217-224. https://doi.org/10.1007/s11046-007-9048-3
  • Kuzay D, Dileköz E, Özer Ç. 2022. Effects of thymoquinone in a rat model of reserpine-induced depression. Braz J Pharm Sci, 58: e19847. https://doi.org/10.1590/s2175-97902022e19847
  • Minj E, Upadhayay S, Mehan S. 2021. Nrf2/HO-1 signaling activator acetyl-11-keto-β-boswellic acid (AKBA)-mediated neuroprotection in methyl mercury-induced experimental model of ALS. Neurochem Res, 46: 2867-2884. https://doi.org/10.1007/s11064-021-03374-y
  • Miranda KM, Espey MG, Wink DA. 2001. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide, 5(1): 62-71. https://doi.org/10.1006/niox.2000.0319
  • Nath KA, Croatt AJ, Likely S, Behrens TW, Warden D. 1996. Renal oxidant injury and oxidant response induced by mercury. Kidney Int, 50: 1032-1043. https://doi.org/10.1038/ki.1996.390
  • Olczak M, Duszczyk M, Mierzejewski M, Meyza K, Majewska MD. 2011. Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats. Behav Brain Res, 223: 107-118. https://doi.org/10.1016/j.bbr.2011.04.036
  • Owumi S, Otunla M, Akindipe P, Oluwawibe B, Babalola JA, Chimezie J, Arunsi U, Owoeye O, Oyelere AK. 2025. Thymoquinone modulates oxidative stress and inflammation, correcting mercury-induced HO-1/NRF/Trx pathway disruption in experimental rat hepatorenal system: An in vivo and in silico study. Biometals, 38: 1179-1202. https://doi.org/10.1007/s10534-025-00699-1
  • Ramachandran S, Thangarajan S. 2016. A novel therapeutic application of solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) on 3-nitropropionic acid induced Huntington’s disease-like symptoms in Wistar rats. Chem Biol Interact, 256: 25-36. https://doi.org/10.1016/j.cbi.2016.06.027
  • Ramachandran S, Thangarajan S. 2018. Thymoquinone loaded solid lipid nanoparticles counteracts 3-nitropropionic acid induced motor impairments and neuroinflammation in rat model of Huntington’s disease. Metab Brain Dis, 33: 1459-1470. https://doi.org/10.1007/s11011-018-0257-6
  • Saleh HA, Abd El-Aziz GS, Mustafa HN, El-Fark M, Mal A, Aburas M, Deifalla AH. 2019. Thymoquinone ameliorates oxidative damage and histopathological changes of developing brain neurotoxicity. J Histotechnol, 42(3): 116-127. https://doi.org/10.1080/01478885.2019.1586344
  • Shandilya A, Mehan S, Kumar S, Sethi P, Narula AS, Alshammari A, Alharbi M, Alasmar AF. 2022. Activation of IGF-1/GLP-1 signalling via 4-hydroxyisoleucine prevents motor neuron impairments in experimental ALS rats exposed to methylmercury-induced neurotoxicity. Molecules, 27: 3878. https://doi.org/10.3390/molecules27123878
  • Yavuz CI. 2020. Çevresel cıva maruz kalımı ve sağlık etkileri. Turk J Public Health, 18(2): 204-217. https://doi.org/10.20518/tjph.710343
  • Zhang H, Wang S, Wang Y, Lu A, Hu C, Yan C. 2021. DHA ameliorates MeHg-induced PC12 cell apoptosis by inhibiting the ROS/JNK signaling pathway. Mol Med Rep, 24: 558. https://doi.org/10.3892/mmr.2021.12228

Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-exposed Rats

Year 2025, Volume: 8 Issue: 5, 182 - 189, 15.09.2025

Dilek Kuzay

https://doi.org/10.19127/bshealthscience.1698368

Abstract

Mercury (Hg) is widely used in nature. It is a substance that has toxic effects even in small amounts. Thymoquinone (TQ) is the main active phenolic compound obtained from the essential oil of Nigella sativa L. (black cumin) seed. The protective effects of TQ against diseases and toxic compounds have been studied for a long time. Aim: This study aimed to investigate the effect of TQ on oxidative stress and behavior in rats exposed to mercury. In this study, 24 adult male Wistar Albino rats weighing between 250±20 g were used. 5 mg/kg Hg and 10 mg/kg TQ were given via intragastric gavage for 21 days. Animals were randomly divided into four groups. Group 1 is the Control, Group 2 TQ (10 mg/kg), Group 3 Hg (5 mg/kg), Group 4 Hg (5 mg/kg) + TQ (10 mg/kg). Open field test and forced swimming test were performed to examine locomotor activity, anxiety, and depression-like behaviors in rats. At the end of the experiment, Malondialdehyde (MDA), total nitric oxide (NO), and reduced glutathione (GSH/RSH) levels were examined in cerebral cortex and plasma. In the open field test, Hg+TQ treatment increased the number of crossings and time spent in the center (P<0.01). In the forced swim test, Hg+TQ treatment increased the swimming and climbing time (respectively P<0.01, P<0.001) and decreased the immobility time (P=0.001). In cerebral cortex and plasma, TQ treatment decreased the increased MDA and NO levels (p=0.01) and increased the decreased GSH/RSH levels (P<0.01) as a result of Hg exposure. Mercury exposure increased oxidative stress in plasma and cerebral cortex, causing anxiety and depression-like behaviors. TQ is can be used to improve some behavioral changes and reduce oxidative stress in Hg-exposed rats.

Keywords

Mercury Behavior Oxidative stress Nigella sativa Rats Antioxidants

Ethical Statement

The experimental procedures were approved by the Local Animal Care and Ethics Committee of Kırşehir Ahi Evran University, (approval date: March 18, 2024, protocol code: 68429034/04).

Supporting Institution

Kırşehir Ahi Evran Üniversitesi

Project Number

This study was supported by Institutional Scientific Research Projects. The Project number is TIP.A3.24.011.

Thanks

This study was supported by Institutional Scientific Research Projects. The Project number is TIP.A3.24.011.

References

  • Abu-Elfotuh K, Abdel-Sattar SA, Abbas AN, Mahran YF, Alshanwani AR, Hamdan AME, Atwa AM, Reda E, Ahmed YM, Zaghlool SS, El-Din MN. 2023. The protective effect of thymoquinone or/and thymol against monosodium glutamate-induced attention-deficit/hyperactivity disorder (ADHD)-like behavior in rats: Modulation of Nrf2/HO-1, TLR4/NF-κB/NLRP3/caspase-1 and Wnt/β-catenin signaling pathways in rat model. Biomed Pharmacother, 162: 114735. https://doi.org/10.1016/j.biopha.2023.114735
  • Akarsu GD, Çetin A. 2022. The effect of thymoquinone on oxidative stress parameters and apolipoprotein E in Alzheimer model in rats. Dement Geriatr Cogn Disord, 51(4): 297-309. https://doi.org/10.1159/000522644
  • Aquib M, Najmi AK, Akhtar M. 2015. Antidepressant effect of thymoquinone in animal models of depression. Drug Res (Stuttg), 65(9):490-494. https://doi.org/10.1055/s-0034-1395621
  • Aykaç G, Uysal M, Yalçın AS, Koçak-Toker N, Sivas A, Oz H. 1985. The effects of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicol, 36: 71-76. https://doi.org/10.1016/0300-483X(85)90128-1
  • Barber SC, Shaw PJ. 2010. Oxidative stress in ALS: Key role in motor neuron injury and therapeutic target. Free Radic Biol Med, 48: 629-641. https://doi.org/10.1016/j.freeradbiomed.2009.11.018
  • Brocardo PS, Boehme F, Patten A, Cox A, Gil-Mohapel J, Christie BR. 2012. Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: Protective effects of voluntary physical exercise. Neuropharmacology, 62: 1607-1618. https://doi.org/10.1016/j.neuropharm.2011.10.006
  • Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. 1986. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol, 123: 520-531.
  • Firdaus F, Zafeer MF, Ahmad M, Afzal M. 2018. Anxiolytic and anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats. Heliyon, 4(6): e00650. https://doi.org/10.1016/j.heliyon.2018.e00650
  • Fouda AM, Daba MY, Dahab GM, Sharaf el-Din OA. 2008. Thymoquinone ameliorates renal oxidative damage and proliferative response induced by mercuric chloride in rats. Basic Clin Pharmacol Toxicol, 103(2): 109-118. https://doi.org/10.1111/j.1742-7843.2008.00267.x
  • Gstraunthaler G, Pfaller W, Kotanko P. 1983. Glutathione depletion and in vitro lipid peroxidation in mercury- or maleate-induced acute renal failure. Biochem Pharmacol, 32: 2969-2972. https://doi.org/10.1016/0006-2952(83)90513-4
  • Kurtel H, Granger DM, Tso P, Grisham MB. 1992. Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Physiol, 263(4 Pt 1): G573-G578. https://doi.org/10.1152/ajpgi.1992.263.4.G573
  • Kustimur S, Kalkanci A, Akbulut G, Gonul B, Bulduk E, Aksakal FN, Yetkin I. 2007. The effect of vaginal candidiasis on the levels of oxidative biomarkers in plasma and tissue samples of diabetic rats. Mycopathologia, 164(5): 217-224. https://doi.org/10.1007/s11046-007-9048-3
  • Kuzay D, Dileköz E, Özer Ç. 2022. Effects of thymoquinone in a rat model of reserpine-induced depression. Braz J Pharm Sci, 58: e19847. https://doi.org/10.1590/s2175-97902022e19847
  • Minj E, Upadhayay S, Mehan S. 2021. Nrf2/HO-1 signaling activator acetyl-11-keto-β-boswellic acid (AKBA)-mediated neuroprotection in methyl mercury-induced experimental model of ALS. Neurochem Res, 46: 2867-2884. https://doi.org/10.1007/s11064-021-03374-y
  • Miranda KM, Espey MG, Wink DA. 2001. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide, 5(1): 62-71. https://doi.org/10.1006/niox.2000.0319
  • Nath KA, Croatt AJ, Likely S, Behrens TW, Warden D. 1996. Renal oxidant injury and oxidant response induced by mercury. Kidney Int, 50: 1032-1043. https://doi.org/10.1038/ki.1996.390
  • Olczak M, Duszczyk M, Mierzejewski M, Meyza K, Majewska MD. 2011. Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats. Behav Brain Res, 223: 107-118. https://doi.org/10.1016/j.bbr.2011.04.036
  • Owumi S, Otunla M, Akindipe P, Oluwawibe B, Babalola JA, Chimezie J, Arunsi U, Owoeye O, Oyelere AK. 2025. Thymoquinone modulates oxidative stress and inflammation, correcting mercury-induced HO-1/NRF/Trx pathway disruption in experimental rat hepatorenal system: An in vivo and in silico study. Biometals, 38: 1179-1202. https://doi.org/10.1007/s10534-025-00699-1
  • Ramachandran S, Thangarajan S. 2016. A novel therapeutic application of solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) on 3-nitropropionic acid induced Huntington’s disease-like symptoms in Wistar rats. Chem Biol Interact, 256: 25-36. https://doi.org/10.1016/j.cbi.2016.06.027
  • Ramachandran S, Thangarajan S. 2018. Thymoquinone loaded solid lipid nanoparticles counteracts 3-nitropropionic acid induced motor impairments and neuroinflammation in rat model of Huntington’s disease. Metab Brain Dis, 33: 1459-1470. https://doi.org/10.1007/s11011-018-0257-6
  • Saleh HA, Abd El-Aziz GS, Mustafa HN, El-Fark M, Mal A, Aburas M, Deifalla AH. 2019. Thymoquinone ameliorates oxidative damage and histopathological changes of developing brain neurotoxicity. J Histotechnol, 42(3): 116-127. https://doi.org/10.1080/01478885.2019.1586344
  • Shandilya A, Mehan S, Kumar S, Sethi P, Narula AS, Alshammari A, Alharbi M, Alasmar AF. 2022. Activation of IGF-1/GLP-1 signalling via 4-hydroxyisoleucine prevents motor neuron impairments in experimental ALS rats exposed to methylmercury-induced neurotoxicity. Molecules, 27: 3878. https://doi.org/10.3390/molecules27123878
  • Yavuz CI. 2020. Çevresel cıva maruz kalımı ve sağlık etkileri. Turk J Public Health, 18(2): 204-217. https://doi.org/10.20518/tjph.710343
  • Zhang H, Wang S, Wang Y, Lu A, Hu C, Yan C. 2021. DHA ameliorates MeHg-induced PC12 cell apoptosis by inhibiting the ROS/JNK signaling pathway. Mol Med Rep, 24: 558. https://doi.org/10.3892/mmr.2021.12228
There are 24 citations in total.

Details

Primary Language English
Subjects Toxicology
Journal Section Research Article
Authors

Dilek Kuzay 0000-0002-1460-9883

Project Number This study was supported by Institutional Scientific Research Projects. The Project number is TIP.A3.24.011.
Publication Date September 15, 2025
Submission Date May 14, 2025
Acceptance Date August 1, 2025
Published in Issue Year 2025 Volume: 8 Issue: 5

Cite

APA Kuzay, D. (2025). Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-exposed Rats. Black Sea Journal of Health Science, 8(5), 182-189. https://doi.org/10.19127/bshealthscience.1698368
AMA Kuzay D. Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-exposed Rats. BSJ Health Sci. September 2025;8(5):182-189. doi:10.19127/bshealthscience.1698368
Chicago Kuzay, Dilek. “Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-Exposed Rats”. Black Sea Journal of Health Science 8, no. 5 (September 2025): 182-89. https://doi.org/10.19127/bshealthscience.1698368.
EndNote Kuzay D (September 1, 2025) Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-exposed Rats. Black Sea Journal of Health Science 8 5 182–189.
IEEE D. Kuzay, “Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-exposed Rats”, BSJ Health Sci., vol. 8, no. 5, pp. 182–189, 2025, doi: 10.19127/bshealthscience.1698368.
ISNAD Kuzay, Dilek. “Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-Exposed Rats”. Black Sea Journal of Health Science 8/5 (September2025), 182-189. https://doi.org/10.19127/bshealthscience.1698368.
JAMA Kuzay D. Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-exposed Rats. BSJ Health Sci. 2025;8:182–189.
MLA Kuzay, Dilek. “Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-Exposed Rats”. Black Sea Journal of Health Science, vol. 8, no. 5, 2025, pp. 182-9, doi:10.19127/bshealthscience.1698368.
Vancouver Kuzay D. Effects of Thymoquinone on Oxidative Stress and Behavior in Mercury-exposed Rats. BSJ Health Sci. 2025;8(5):182-9.
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