Atrazine, as an herbicide, is used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, atrazine exposure is a potential threat to human health. The present study evaluated the possible protective effects of zinc oxide nanoparticles and vitamin C against atrazine-induced hepatotoxicity in rats. Atrazine administered to rats orally at a dose of 300 mg/kg for 21 days caused liver oxidative stress as it increased malondialdehyde (MDA) formation and decreased reduced glutathione (GSH) contents. Atrazine induced inflammation accompanied by apoptosis via upregulation of hepatic gene expression levels of NF-κB, TNF-α, BAX, and caspase-3 and downregulation of Bcl-2 gene expression levels. Additionally, it disturbed the metabolic activities of cytochrome P450 as it downregulated hepatic gene expression levels of CYP1A1, CYP1B1, CYP2E1. The liver function biomarkers were greatly affected upon atrazine administration, and the serum levels of AST and ALT were significantly increased, while BWG%, albumin, globulins, and total proteins levels were markedly decreased. As a result of the above-mentioned influences of atrazine, histopathological changes in liver tissue were recorded in our findings. The administration of zinc oxide nanoparticles or vitamin C orally at a dose of 10 mg/kg and 200 mg/kg, respectively, for 30 days prior and along with atrazine, could significantly ameliorate the oxidative stress, inflammation, and apoptosis induced by atrazine and regulated the hepatic cytochrome P450 activities. Furthermore, they improved liver function biomarkers and histopathology. In conclusion, our results revealed that zinc oxide nanoparticles and vitamin C supplementations could effectively protect against atrazine-induced hepatotoxicity.

Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article, we reported the synthesis of a series of new hybrid molecules through merging the structural features of chalcones and pyridothienopyrimidinones. Our results indicated that the synthesis of chalcone‐thienopyrimidine derivatives from the corresponding thienopyrimidine and chalcones proceeded in a relatively short reaction time with good yields and high purity. Most of these novel compounds exhibited moderate to robust cytotoxicity against HepG2 and MCF‐7 cancer cells similar to that of 5‐fluorouracil (5‐FU). The results indicated that IC₅₀ of the two compounds (3b and 3g) showed more potent anticancer activities against HepG2 and MCF‐7 than 5‐FU. An MTT assay and flow cytometry showed that only 3b and 3g had anticancer activity and antiproliferative activities at the G1 phase against MCF‐7 cells, while six compounds (3a‐e and 3g) had cytotoxicity and cell cycle arrest at different phases against HepG2 cells. Their cytotoxicity was achieved through downregulation of Bcl‐2 and upregulation of Bax, caspase‐3, and caspase‐9. Although all tested compounds increased oxidative stress via increment of MDA levels and decrement of glutathione reductase (GR) activities compared to control, the 3a, 3b, and 3g in HepG2 and 3b and 3g in MCF‐7 achieved the target results. Moreover, there was a positive correlation between cytotoxic efficacy of the compound and apoptosis in both HepG2 (R² = 0.531; P = 0.001) and MCF‐7 (R² = 0.219; P = 0.349) cell lines. The results of molecular docking analysis of 3a-g into the binding groove of Bcl‐2 revealed relatively moderate binding free energies compared to the selective Bcl‐2 inhibitor, DRO. Like venetoclax, compounds 3a-g showed 2 violations from Lipinski’s rule. However, the results of the ADME study also revealed higher drug‐likeness scores for compounds 3a-g than for venetoclax. In conclusion, the tested newly synthesized chalcone‐pyridothienopyrimidinone derivatives showed promising antiproliferative and apoptotic effects. Mechanistically, the compounds increased ROS production with concomitant cell cycle arrest and apoptosis. Therefore, regulation of the cell cycle and apoptosis are possible targets for anticancer therapy. The tested compounds could be potent anticancer agents to be tested in future clinical trials after extensive pharmacodynamic, pharmacokinetic, and toxicity profile investigations.

Nicotine is the major alkaloid present in cigarettes that induces various biochemical and behavioral changes. Nanonaringenin (NNG) and vitamin E are antioxidants that are reported to mitigate serious impairments caused by some toxins and oxidants. Thus, we aimed to investigate the efficacy of NNG, vitamin E, and their combinations to ameliorate behavioral, biochemical, and histological alterations induced by nicotine in rats. Adult male albino rats were randomly grouped into six equal groups (10 rats/group): control, N (nicotine 1mg/kg b.w./day S/C from 15^th to 45^th day, 5 days a week), NNG (25mg/kg b.w./day orally for 45 days), N+NNG, N+E (nicotine+vitamin E 200mg/kg b.w./day orally), and N+NNG+E (nicotine+NNG+vitamin E at the aforementioned doses). Behavioral tests were conducted on day 15 and 30 postnicotine injection, while memory tests, brain neurotransmitters, antioxidants, and histopathological examination were examined at day 30 only. As a result, nicotine impaired rats activity (hypoactivity and hyperactivity) and memory, induced anxiolytic and anxiogenic effects on rats, and altered neurotransmitters (acetylcholinesterase, serotonin, and dopamine), and redox markers (MDA, H₂O₂, GSH, and catalase) levels in brain homogenates. Thickening and congestion of the meninges and degeneration of the cerebral neurons and glia cells were observed. Cosupplementation with NNG, vitamin E, and their combination with nicotine was beneficial in the alleviation of activity impairments and improved short memory and cognition defects and exploratory behaviors. Our results indicate the antioxidant potential of NNG and vitamin E by modulating redox markers and neurotransmitters in the brain. Thus, data suggest that the prophylactic use of NNG, vitamin E, and/or their combination for (45 days) may have a successful amelioration of the disrupted behavior and cognition and biochemical and histopathological alterations induced by nicotine.

| This research evaluates the biochemical effect of adding 7% olive cake as feed additives on lipid profile, fatty acids, antioxidants concentrations in serum and/or egg yolk and on gene expression of fatty acid synthase and acetyl CoA carboxylase in laying hens. The experiment was applied on 42 Commercial Mandarah strain laying hens which divided equally into control and olive cake (7%) group. Addition of olive cake (7%) led to a significant increase in serum and egg yolk HDL-C and a significant decrease in TAG, cholesterol, LDL-C and VLDL concentrations. SOD, GSH and TAC concentrations were significantly increased in serum and egg yolk in olive cake group, while MDA and NO were significantly decreased. Hens fed 7% olive cake recorded a significant increase in the concentration of oleic, linoleic and linolenic with a significant decrease in stearic in egg yolk. In breast muscle the concentration of oleic acid was significantly increased while saturated concentrations fatty acids were significantly decreased in olive cake group. Gene expression of FAS and ACC was significantly increased in the olive cake group.