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Objective(s): This study was conducted to explore the impact of 1, 8-cineole (eucalyptol) on the biochemical, molecular, and histological changes caused by lead acetate in the liver of adult male Wistar rats. The research also investigated the potential involvement of the TLR4 signaling pathway in this effect. Materials and Methods: Rats were orally administered lead acetate (25 mg/kg-day) for 14 consecutive days and received 1, 8-cineole (100 mg/kg-day) during the same period. Results: 1, 8-cineole prevented an increase in the malondialdehyde level, a decrease in the glutathione level, and a decrease in the activity of superoxide dismutase and glutathione peroxidase enzymes in the liver of rats treated with lead acetate. This monoterpene also prevented an increase in the expression of pro-inflammatory cytokines and significantly reduced the infiltration of inflammatory cells in the liver parenchyma. Additionally, 1, 8-cineole discouraged the increase in toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) expression in the liver and stopped a rise in serum AST and ALT enzymes. Conclusion: 1, 8-cineole can prevent liver damage caused by lead acetate by reducing oxidative stress and inflammation. This hepatoprotection is probably achieved by inhibiting TLR4/MyD88/NF-κB signaling. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of the monoterpenes thymol and p‐cymene on the liver of rats subjected to prolonged immobilization stress and to discover the possible mechanism behind this effect. For 14 consecutive days, the rats were placed in a restrainer for 2.5 h every day to expose them to stress. During the same period, thymol (10 mg/kg, gavage) and p‐cymene (50 mg/kg, intraperitoneally) were also administered. Thymol and p‐cymene prevented the increase in malondialdehyde levels and the decrease in glutathione content in the liver of rats exposed to chronic immobility. They also increased the activity of the glutathione peroxidase enzyme in the liver of stressed animals, but only thymol could increase the activity of superoxide dismutase. These monoterpenes reduced the expression of pro‐inflammatory cytokines tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, and IL‐6 and nuclear factor kappa B (NF‐κB) in the liver of stressed animals. They increased the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1). Thymol and p‐cymene greatly prevented the infiltration of inflammatory cells in the liver parenchyma of stressed rats. In conclusion, the study found that thymol and p‐cymene have a hepatoprotective effect on immobilized rats, likely exerted by suppressing oxidative stress and inflammation, stimulating Nrf2/HO‐1 signaling, and inhibiting the TNF‐α/NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Objective(s): Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl4. Materials and Methods: CCl4 was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period. Results: CCl4 increased the level of malondialdehyde (P<0.01 in the kidney and P<0.001 in the testis) and nitric oxide (P<0.001 in the kidney and P<0.01 in the testis) and decreased the levels of glutathione (P<0.05) in the kidneys and testicles of rats. CCl4 also reduced the catalase enzyme activity in the kidneys (P<0.05) but did not affect its activity in the testis. In addition, CCl4 enhanced the mRNA expression of TNF-α (P<0.01), nuclear factor-κB (P<0.05), and Bax (P<0.05 in the kidney and P<0.01 in the testis) and decreased the expression of Bcl-2 (P<0.05) in both organs. Alphapinene prevented all the mentioned changes, but it did not influence the expression of Bcl-2 in the kidneys of rats receiving CCl4. Conclusion: Alpha-pinene may have the potential to prevent renal and testicular diseases by strengthening the antioxidant system in the kidneys and testis, and inhibiting oxidative/nitrosative stress, inflammation, and apoptosis caused by CCl4. [ABSTRACT FROM AUTHOR]

The investigation of the effect of carvone (a natural monoterpene) on liver damage caused by chronic immobilisation. Male Wistar rats were divided into four groups: control, carvone, stress, and stress-carvone. To induce stress, rats were placed in a restrainer (6 h/21 day) and carvone was treated by gavage at a dose of 20 mg/kg. Alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities were significantly increased in sera of immobilised rats. Chronic immobilisation also increased malondialdehyde levels and decreased reduced glutathione content, as well as increased TNF-α, IL-1β, IL-6, and NF-κB mRNA expression and also led to the infiltration of inflammatory cells in the liver parenchyma. Carvone's 21-day treatment prevented all of these changes in immobilised rats. It is concluded that carvone has effectively prevented chronic immobilisation-induced liver injury, most probably through its antioxidant and anti-inflammatory capabilities. [ABSTRACT FROM AUTHOR]

The research was conducted to examine the neuroprotective effect of thymol and its precursor p-cymene on chronic immobility stress in adult male Wistar rats. The rats were subjected to 2.5 h of stress every day for 14 consecutive days by placing them inside a restrainer. Thymol (10 mg/kg) and p-cymene (50 mg/kg) were given to the rats during the same period. The results showed that thymol and p-cymene prevented the increase of MDA level, decline of GSH level, and decrease of SOD and GPx activity in the hippocampus of rats exposed to stress. These monoterpenes also prevented the increase in the expression of Tnfa, Il1b, Tlr4, and Nfkb, and the decrease in the expression of Nrf2, Ho1, and Bdnf. In addition, thymol and p-cymene inhibited the increase in the expression and activity of acetylcholinesterase in the hippocampus of animals exposed to immobility and enhanced the expression of A7nachr. They also reduced neuronal death in the CA1 region of stressed animals and improved their performance in the Morris water maze and elevated plus maze tests. Based on these findings, thymol and p-cymene may be effective in preventing neurodegenerative diseases as they reduce oxidative stress and neuroinflammation, strengthen ACh signaling, and stimulate Bdnf expression., Competing Interests: Declarations Ethics Approval All experiments were carried out according to the standard international guidelines for using laboratory animals and were approved by the Animal Ethics Committee at Islamic Azad University, Zanjan Branch (code IR.IAU.Z.REC.1396,23). Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl 4 ., Materials and Methods: CCl 4 was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period., Results: CCl 4 increased the level of malondialdehyde ( P <0.01 in the kidney and P <0.001 in the testis) and nitric oxide ( P <0.001 in the kidney and P <0.01 in the testis) and decreased the levels of glutathione ( P <0.05) in the kidneys and testicles of rats. CCl 4 also reduced the catalase enzyme activity in the kidneys ( P <0.05) but did not affect its activity in the testis. In addition, CCl 4 enhanced the mRNA expression of TNF-α ( P <0.01), nuclear factor-κB (P<0.05), and Bax ( P <0.05 in the kidney and P <0.01 in the testis) and decreased the expression of Bcl-2 ( P <0.05) in both organs. Alpha-pinene prevented all the mentioned changes, but it did not influence the expression of Bcl-2 in the kidneys of rats receiving CCl 4 ., Conclusion: Alpha-pinene may have the potential to prevent renal and testicular diseases by strengthening the antioxidant system in the kidneys and testis, and inhibiting oxidative/nitrosative stress, inflammation, and apoptosis caused by CCl 4 ., Competing Interests: None.

Sphingosine-1 phosphate (S1P) is involved in a variety of cellular processes via activation of S1P receptors (S1PRs; S1PR1 to S1PR5) that are highly expressed in the brain. It has been shown that the level of S1P is reduced in the brain of Alzheimer's disease (AD) patients. However, there is no study designed to evaluate the expression of S1PRs in AD brains. The objectives of the present work are (1) to examine the expression of S1PR1-3 in the hippocampus of beta amyloid (Aβ) 1-42 injected rats and (2) to clarify the effects of chronic S1PR1 activation on S1PR1-3 levels, spatial memory deficit and hippocampal damage in AD rats. SEW2871, the S1PR1 selective agonist, repeatedly was injected intraperitoneally during a period of two weeks. Upon Western Blot data bilateral intrahippocampal injection of Aβ1-42 decreased the expression of S1PR1 while increased S1PR2 level and did not affect that of S1PR3. We found that chronic administration of SEW2871 inhibited the reduction of S1PR1 expression and ameliorated spatial memory impairment in the Morris water maze task in rats. In addition, SEW2871 attenuated the Aβ1-42-induced hippocampal neuronal loss according to Nissl staining findings. Data in the current study highlights the importance of S1PR1 signaling pathway deregulation in AD development and suggests that activation of S1PR1 may represent a potential approach for developing new therapeutics to manage memory deficit and apoptosis associated with neurodegenerative disorders such as AD.