Crude oil extracts, components of extracts, and ethanolic extracts of Inula graveolens possess various pharmacological activities on various cancer cells including antioxidative and antiproliferative effects. Aqueous extract of this species has not been investigated on the liquid malignancies and solid tumors with a high incidence of treatment refractoriness and poor survival outcomes such as glioblastoma and leukemia. Hence, the present study aimed to evaluate the cytotoxic efficiency of I. graveolens aqueous extracts on human glioblastoma multiforme and chronic myelogenous leukemia cell lines in comparison to non-cancerous primary rat cerebral cortex and human peripheral blood mononuclear cells. The cells were treated with the extracts of I. graveolens (125-1000 μg/mL) for 48 h, the cellular viability was identified using 3'-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and lactate dehydrogenase release was measured to determine the cytotoxic potential. Total oxidant status and apurinic/apyrimidinic endodeoxyribonuclease 1 assays were used to determine the oxidative status of cells and DNA damage, respectively. I. graveolens showed selective cytotoxicity toward human glioblastoma multiforme and chronic myelogenous leukemia cell lines and exhibited a higher antiproliferative effect against cancer cells in comparison to non-cancerous cells. Moreover, it significantly reduced the apurinic/apyrimidinic endodeoxyribonuclease 1 levels on both cancer cell lines as compared with their control cells without changing the levels of an oxidative stress marker. The extracts of I. graveolens have anti-cancer potential on human glioblastoma multiforme and chronic myelogenous leukemia cell lines without causing oxidative stress.

One of the side effects of hydroxychloroquine is ototoxicity. This study examined the effect of adenosine triphosphate (ATP) on ototoxicity in rats treated with hydroxychloroquine (HCQ). In this study, 24 rats (male, albino Wistar) were used. The animals were divided into four groups: healthy control group (HG), ATP alone group (ATPG), HCQ alone group (HCQG), and ATP + HCQ (AHQG) group. The ATPG and AHQG groups were injected with ATP intraperitoneally (IP) at a dose of 4 mg/kg/day. The HG and HCQG groups were treated with the same volume of saline as the solvent by IP route. The AHQG group was administered HCQ orally at a dose of 120 mg/kg/day 1 h after the ATP and saline administration. This procedure was repeated daily for 10 days. The rats were euthanized (50 mg/kg thiopental sodium, IP) and after, vestibulocochlear nerve tissues were removed and the tissue oxidant and antioxidant parameters were studied. The tissues were also subjected histopathological examination. ATP significantly (p < 0.001) suppressed the increase in malondialdehyde associated with HCQ in vestibulocochlear nerve tissues as well as the decrease in total glutathione, superoxide dismutase, and catalase levels. ATP also reduced the severity of oedema, vascular congestion, dilatation, and collagen deposition in degenerated myelinated nerve fibers associated with HCQ. ATP is effective against oxidative damage associated with HCQ in vestibulocochlear nerve tissue.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib are widely used in non-small-cell lung cancer treatment, and accumulating evidence indicates they can markedly increase ocular toxicity. Nonetheless, whether erlotinib causes optic nerve injury has not been investigated before and remains a subject worth investigating. This study aimed to examine the impact of erlotinib on oxidative stress, inflammation, and histopathological changes in rat optic nerve tissue and evaluate the potential neuroprotective role of thiamine pyrophosphate (TPP). Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control, TPP alone, erlotinib alone, and erlotinib + TPP. Erlotinib (10 mg/kg, orally, on alternate days) and TPP (20 mg/kg, intraperitoneally, daily) were administered for two consecutive weeks. Optic nerve samples were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), followed by histopathological examination. Results: Erlotinib treatment significantly increased MDA, IL-1β, and TNF-α levels while reducing tGSH, SOD, and CAT activity, demonstrating oxidative stress and an inflammatory response. Co-administration of TPP ameliorated these changes by lowering reactive oxygen species, restoring antioxidant capacity, and attenuating inflammation. Histopathological alterations, including astrocyte degeneration, edema, and vascular congestion, were evident after erlotinib exposure but were significantly alleviated when TPP was administered concurrently. Conclusions: Erlotinib induces oxidative and inflammatory optic nerve injury, while TPP co-treatment offers significant neuroprotection. These findings support TPP as a potential adjunct to reduce EGFR-TKI-related ocular toxicity and highlight importance of redox modulation in limiting treatment-associated side effects.

This study investigates the protective role of Hispidulin on acute respiratory distress syndrome (ARDS) in rats. Rats were divided into three groups: control, ARDS, ARDS+ Hispidulin. The ARDS models were established by injecting rats with oleic acid. Hispidulin (100 mg/kg) was injected i.p. an hour before ARDS. Myeloperoxidase (MPO), Interleukin-8 (IL-8), Mitogen-activated protein kinases (MAPK), Lipid Peroxidation (LPO), Superoxide Dismutase (SOD), Glutathione (GSH), and Angiotensin-converting enzyme (ACE) were determined by ELISA. Tumor necrosis factor-alpha (TNF-α) expression was described by RT-qPCR. Caspase-3 immunostaining was performed to evaluate apoptosis. Compared with the model group, a significant decrease was observed in the MPO, IL-8, MAPK, ACE, LPO levels, and TNF-α expression in the ARDS+ Hispidulin group. Moreover, reduced caspase-3 immunoreactivity and activity of ACE were detected in the Hispidulin+ARDS group. The protective effect of Hispidulin treatment may act through inhibition of the ACE activity and then regulation of inflammatory cytokine level and alteration of apoptosis.

Purpose: In this study, our aim was to investigate the potential effects of strong antioxidant daidzein (DZ) on ovarian ischemia and reperfusion injury. Materials and Methods: A total of 42 female Sprague-Dawley rats were randomly divided into seven groups. For the experimental model, the clamps were removed after 3 hours of ischemia, and blood flow was provided again. Then, reperfusion process was terminated for 3 hours. Daidzein was orally administered to animals at doses of 35 and 70 mg/kg 30 minutes before ischemia (I) and ischemia and reperfusion (I/R) procedures. Results: Severe immunoreactivity of the IL-1β, IL-6 and Caspase-3 were detected in I and I/R groups. Moderate immunoreactivity of IL-1β, IL-6 and Caspase-3 was detected in I+DZ35 and I/R+DZ35 groups, and slightly positivity was detected in I+DZ70 and I/R+DZ70 groups. The SOD activity level increased in the groups treated with Daidzein, while MDA levels decreased. In addition, hemorrhage areas and inflammatory cell migration decreased in I/R+DZ70 and I/R+DZ35 groups, when compared to I/R group in a dose dependent manner. Conclusion: Daidzein has a strong protective role in the treatment of ovarian ischemia-reperfusion injury and can be used as a therapeutic agent.