Human & Experimental Toxicology

Mamyrbayev, Arstan; Baitenov, Kuanysh; Komekbay, Zhanat; Kaliev, Abdiraman; Bermagambetova, Saule; Sakhanova, Svetlana; Shayakhmetova, Kulyan; Karashova, Gulsim

doi: 10.1177/09603271251377601pmid: 40994039

IntroductionThis study aimed to assess the acute toxic properties of drilling fluid (DF), a multicomponent substance extensively utilized in oil extraction, through a single intragastric administration in mature male rats, to better understand its potential health risks.MethodsAcute toxicity was evaluated in mature male rats via a single intragastric administration of DF at doses of 300, 600, 1200, 2400, and 4800 mg/kg. Mortality, body weight changes, and relative organ weights were monitored throughout the study. Biochemical enzyme activities, including ALT, AST, ALP, and LDH, were assessed. Behavioral responses were recorded, and histological examinations of the liver, kidneys, and heart were conducted to evaluate tissue-level effects.ResultsAdministration of DF caused significant toxic effects including mortality (2 deaths at 2400 mg/kg; 3 deaths at 4800 mg/kg), changes in body weight, and relative weights of liver (control: 7.12 ± 0.53; 2400 mg/kg: 7.89 ± 0.51; 4800 mg/kg: 9.68 ± 0.67; p < 0.001) and heart (control: 1.24 ± 0.17; 2400 mg/kg: 0.97 ± 0.21; 4800 mg/kg: 0.84 ± 0.08; p < 0.001). Activities of cytolytic enzymes ALT (control: 78.65 ± 4.28; 4800 mg/kg: 89.47 ± 2.62; p < 0.001) and AST (control: 226.18 ± 31.66; 4800 mg/kg: 322.73 ± 8.02; p < 0.001), as well as ALP and LDH, were significantly altered. Behavioral activity was markedly reduced. Histological changes were observed in the liver, kidneys, and heart tissues.DiscussionThese findings demonstrate that DF exhibits marked acute toxicity and causes significant physiological and histopathological damage in mammals, indicating a potential hazard.

Hosseini, Seyed Ershad; Shiri, Elham; Nosrati, Shiva; Ramezani-Aliakbari, Khadijeh; Salehi, Iraj; Shokri, Farid; Ramezani-Aliakbari, Fatemeh

doi: 10.1177/09603271251377329pmid: 40911476

IntroductionVitamin D overdose, often stemming from excessive supplementation rather than dietary intake. It has been associated with various conditions such as cardiovascular disorders. This study aimed to investigate the effects of vitamin D toxicity on cardiac tissue.MethodsSixteen Wistar rats (250 ± 50 g) were randomly divided into two groups: the control group and the high-dose vitamin D group (40,000 IU/kg). Vitamin D was administered via gavage for 8 weeks. The expression of sirtuin 1 (SIRT1), the peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1-α), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) genes in cardiac tissue was evaluated. Blood samples were analysed for lactate dehydrogenase (LDH) levels. Moreover, oxidative stress markers, including malondialdehyde (MDA) and superoxide dismutase (SOD), were measured in tissue samples. Histopathological evaluations were also conducted.ResultsThe expression of SIRT1, PGC1-α, Bcl-2, and the SOD levels were significantly decreased in the vitamin D-treated group. In addition, the values indicated a significant increase in the expression of Bax along with LDH and MDA levels in the vitamin D-treated group compared to the control group.DiscussionLong-term administration of high-dose vitamin D significantly increased oxidative stress and apoptosis in cardiac tissue, likely mediated by the SIRT1/PGC1-α pathway.Graphical abstractThe illustration of the suggested mechanism underlying high-dose vitamin D-induced cardiotoxicity.

Mamyrbayev, Arstan; Zhurgenova, Altynay; Komekbay, Zhanat; Kaliev, Abdiraman; Zhilisbayeva, Kulyash; Yerimbetova, Gulmira; Satybaldiyeva, Umit; Bermagambetova, Saule; Sakhanova, Svetlana

doi: 10.1177/09603271251379839pmid: 40994012

IntroductionThis study investigates the skin-irritating and skin-resorptive effects of drilling fluid (DF) through acute and subacute experiments conducted on adult rabbits and sexually mature male and female rats.MethodsAcute and subacute experiments were conducted on adult rabbits and sexually mature male and female rats. The acute experiment involved a single exposure to DF, while the subacute study involved repeated dermal exposure. Various physiological, biochemical, and histopathological assessments were performed to evaluate the effects.ResultsThe results of the acute experiment demonstrated that DF exhibits a mild skin-irritating effect but causes significant irritation to the ocular mucous membranes in rabbits. In the subacute study, dermal exposure to DF led to notable alterations in the physiological and biochemical status of rats, including reduced food and water intake, decreased body weight gain, and significant changes in hematological and biochemical parameters. An increase in the relative count of certain leukocyte populations was observed, with a statistically significant elevation in absolute eosinophil counts in both sexes. Similar trends were observed for basophils and lymphocytes. Moderate elevations in serum enzyme levels (ALT, AST, ALP, GGT, and LDH) indicated systemic toxicity. Morphological and morphometric analysis of the skin further supported the dermal toxicity of DF, revealing epidermal keratinization, marked proliferation of germinative layer cells, and cellular heterotopia. In the basal layer of the epidermis, cells exhibited signs of intracellular edema. The papillary layer showed moderate focal inflammatory infiltrates, while the reticular dermis displayed edema of fibrous structures, swelling of collagen fibers, and increased fiber thickness.DiscussionThese findings collectively demonstrate that the tested drilling fluid possesses significant dermal and systemic toxicity, indicating potential health risks for mammals upon repeated exposure.