Thymoquinone could be protective against valproic acid‐induced testicular toxicity by antioxidant and anti‐inflammatory mechanisms

Savran, Mehtap; Aşçı, Halil; Armağan, İlkay; Erzurumlu, Yalçın; Azırak, Sebile; Özer, Mehmet Kaya; Bilğiç, Sedat; Korkmaz, Deniz Taştemir

doi:10.1111/and.13623

Cited by 17 publications

(8 citation statements)

References 45 publications

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“…In this study, ROS, TOS, and OSI levels in VPA given group were remarkably elevated, while TAS levels notably decreased compared to control rats. Current outcomes were in harmony with the findings of Savran et al [28], who reported that an increase in TOS levels was concomitant to a decrease in TAS levels, thus increasing OSI levels in VPA-mediated in testicular toxicity. It was shown that TOS levels remarkably increased whereas TAS levels notably decreased in children with seizures taking sixty days on VPA monotherapy [29].…”

Section: Discussionsupporting

confidence: 87%

Protective effect of edaravone on rat testis after valproic acid treatment

CELIK¹,

Bayrak²,

Cakmak³

et al. 2022

jrp

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Valproic acid (n-dipropyl-acetic acid, VPA) is a medication used as anticonvulsant in the treatment of bipolar disorder, and for migraine prophylaxis. Long-term use of VPA is known to trigger reproductive impairment, which is mediated by elevation of testicular oxidative stress. Edaravone is used in the treatment of cerebrovascular diseases. It can diffuse into many disease-affected organs, thus shows protective effects in numerous tissues including the heart, lung, and testis. The main goal of the present study was to determine the possible protective role of edaravone against VPA-induced oxidative testicular injury. Male Sprague Dawley rats were assigned into four groups. Control rats; rats given only edaravone (30 mg/kg/day); rats given only VPA (500 mg/kg/day); rats given VPA+edaravone for seven days. Edaravone and VPA were applied intraperitoneally. After eight days, testicular tissues were taken from rats. There was a statistically significant increase in the levels of reduced glutathione, lipid peroxidation, reactive oxygen species, total oxidant status, oxidative stress index, and DNA contents as well as catalase, superoxide dismutase, glutathione-related enzymes, gamma-glutamyl transferase, acid and alkaline phosphatases, lactate dehydrogenase, myeloperoxidase and sorbitol dehydrogenase activities in VPA group. More so, advanced oxidized protein products, protein carbonyl, and nitric oxide levels were also significantly increased in VPA group. Activities of glucose-6phosphate dehydrogenase and sodium/potassium ATPase and total antioxidant status levels remarkably decreased in VPA given group. Treatment with edaravone to VPA group significantly reverted these alterations. These findings demonstrate that administration of edaravone has a beneficial effect against testicular injury in VPA-induced oxidative stress.

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Section: Discussionsupporting

confidence: 87%

Protective effect of edaravone on rat testis after valproic acid treatment

CELIK¹,

Bayrak²,

Cakmak³

et al. 2022

jrp

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“…Studies have reported that TQ can increase cellular antioxidants and can upregulate SOD, CAT, and GPx genes in a dosedependent manner. [39][40][41] In our study, TQ treatment markedly improved the cellular antioxidant levels suggesting its antilipid peroxidative effect.…”

Section: Tq Treatment Suppresses Proliferation Of Lung Alveolar Epith...supporting

confidence: 65%

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene‐induced experimental lung cancer

Nithya

Rajasekaran

Vanitha

et al. 2022

J Biochem & Molecular Tox

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Several studies have suggested that increased consumption of phytochemicals is a comparatively easy and practical strategy to significantly decrease the incidence of cancer. In the present study, we have reported the protective effect of a natural compound, thymoquinone (TQ) against benzo(a)pyrene (B(a)P)‐induced lung carcinogenesis in Swiss albino mice. B(a)P (50 mg/kg body weight) was administered twice weekly for four successive weeks and left until 20 weeks to induce lung cancer in mice. TQ (20 mg/kg body weight) was given orally as a pretreatment and posttreatment drug to determine its chemopreventive and therapeutic effects. B(a)P‐induced lung cancer‐bearing animals displayed cachexia‐like symptoms along with an abnormal increase in lung weight and the activities of marker enzymes adenosine deaminase, aryl hydrocarbon hydroxylase, gamma‐glutamyl transpeptidase, 5′‐nucleotidase and lactate dehydrogenase; tumor marker carcinoembryonic antigen levels. Furthermore, B(a)P‐induced animals showed elevated levels of lipid peroxides with subsequent depletion in the antioxidant status and histological aberrations. These anomalies were accompanied by increased expressions of proliferating cell nuclear antigen and cyclin D1 in the lung sections derived from B(a)P‐induced animals. On TQ treatment, all the above alterations were returned to near normalcy. Furthermore, TQ administration in B(a)P‐induced animals downregulated phosphatidylinositol 3‐kinase/protein kinase B signaling pathway and induced apoptosis as evidenced by a decrease in cytochrome c, proapoptotic Bax, caspase‐3, and p53 with a parallel increase in antiapoptotic Bcl‐2. Our present results demonstrate the potential effectiveness of TQ as an antioxidant, antiproliferative, and apoptotic agent against B(a)P‐induced experimental lung tumorigenesis.

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“…This status prevents the immediate toxic effects of the cationic (free) cadmium and scavenges free radicals generated during the cadmium exposure (Moradkhani et al, 2020;Ruttkay-Nedecky et al, 2013). Zeinvand-Lorestani et al, 2018), kidney (Abdel-Daim et al, 2020;Ozer et al, 2020), and testis (Öztürk et al, 2020;Savran et al, 2020), against the oxidative stress induced by various xenobiotics. As shown in Table 1, several studies show that cadmium weakens the cell's antioxidant defenses, and TQ can prevent the oxidative effects of cadmium by improving the level of intracellular antioxidant markers and inflammatory factors (Erboga et al, 2016;Fouad et al, 2016;Sayed et al, 2014).…”

Section: Cadmium and Oxidative Stressmentioning

confidence: 99%

Protective potential of thymoquinone against cadmium, arsenic, and lead toxicity: A short review with emphasis on oxidative pathways

Ghasemi

Nili‐Ahmadabadi

Omidifar

et al. 2023

J of Applied Toxicology

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Heavy metals are among the most important environmental pollutions used in various industries. Their extensive use has increased human susceptibility to different chronic diseases. Toxic metal exposure, especially cadmium, arsenic, and lead, causes oxidative damages, mitochondrial dysfunction, and genetic and epigenetic modifications. Meanwhile, thymoquinone (TQ) is an effective component of Nigella sativa oil that plays an important role in preventing the destructive effects of heavy metals. The present review discusses how TQ can protect various tissues against oxidative damage of heavy metals. This review is based on the research reported about the protective effects of TQ in the toxicity of heavy metals, approximately the last 10 years (2010–2021). Scientific databases, including Scopus, Web of Science, and PubMed, were searched using the following keywords either alone or in combination: cadmium, arsenic, lead, TQ, and oxidative stress. TQ, as a potent antioxidant, can distribute to cellular compartments and prevent oxidative damage of toxic metals. However, depending on the type of toxic metal and the carrier system used to release TQ in biological systems, its therapeutic dosage range may be varied.

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Thymoquinone could be protective against valproic acid‐induced testicular toxicity by antioxidant and anti‐inflammatory mechanisms

Cited by 17 publications

References 45 publications

Protective effect of edaravone on rat testis after valproic acid treatment

Protective effect of edaravone on rat testis after valproic acid treatment

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene‐induced experimental lung cancer

Protective potential of thymoquinone against cadmium, arsenic, and lead toxicity: A short review with emphasis on oxidative pathways

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