Samar R. Saleh

Exposure to heavy metals and unbalanced diets poses significant global health concerns. This study investigated the neurotoxic effect of chronic lead acetate and high-fat diet (Pb/HFD) co-exposure in rats and the neuroprotective potential of 10-hydroxydecanoic acid (HDA) and zinc oxide nanoparticles (ZnO-NPs). Rats were allocated into naive, HDA, ZnO-NPs, MIX (HDA/ZnO-NPs), Pb/HFD, Pb/HFD + HDA, Pb/HFD + ZnO-NPs, and Pb/HFD + MIX, with 10 rats per group. For 12 weeks, rats received a daily oral dose of PbAc (30 mg/kg) alongside a 40% fat HFD. Following this induction period, groups continued the Pb/HFD exposure for an additional 4 weeks while also receiving a daily dose of either HDA (5 mg/kg), ZnO-NPs (5 mg/kg), or a combination of both. Spatial learning and memory, brain lead content, and key markers of oxidative stress, neuroinflammation, amyloidogenesis, and apoptosis were evaluated. Pb/HFD co-exposure significantly increased brain lead levels, leading to cognitive impairment as evidenced by the Morris water maze test. This was attributed to a rise in oxidative stress, inflammatory responses, and amyloidogenesis, alongside a reduction in antioxidant markers and a proliferation of glial cells. In contrast, HDA effectively mitigated both the cognitive deficits and the underlying neuroinflammation and oxidative stress. Conversely, ZnO-NPs alone were linked to detrimental cognitive effects, primarily through oxidative stress and neuroinflammation. Our findings support a neuroprotective role for HDA and highlight the need for caution regarding ZnO-NPs monotherapy. Critically, the combination of HDA and ZnO-NPs exhibited a synergistic neuroprotective effect, offering a promising and enhanced therapeutic strategy against environmental and dietary neurotoxic stressors.

There has been a significant increase in human exposure to heavy metals (HMs) over the course of the previous century, primarily due to the extensive industrial processes. Male infertility is a prominent complication associated with lead exposure, wherein lead has the potential to accumulate within the testes, resulting in oxidative stress and inflammation. In addition, 10-hydroxydecanoic acid (10-HDA) is a component found in the secretions of worker bees and possesses the capacity to mitigate oxidative stress and prevent inflammation. Due to their advantageous properties, zinc oxide nanoparticles (ZnO-NPs) possess a wide range of applications in the field of biomedicine. This study aimed to assess the therapeutic effect of 10-HDA and ZnO-NPs on testicular toxicity in rats induced by lead acetate (PbAc). PbAc was administered orally for a period of 3 months. Following that, 10-HDA and/or ZnO-NPs were administrated for 1 month. PbAc deformed seminal analysis, decreased seminal fructose and sex hormonal levels, and resulted in the development of histopathological complications. Additionally, PbAc increased MDA and decreased Nrf2 and HO-1 expression, confirmed by the declined antioxidant defense system. Furthermore, an increase in testicular inflammatory markers and the Bax/Bcl-2 ratio was observed subsequent to the administration of PbAc. The administration of 10-HDA and ZnO-NPs demonstrated significant efficacy in the restoration of semen quality, pituitary/gonadal hormones, antioxidants, and testicular histoarchitecture. Moreover, 10-HDA and ZnO-NPs decreased testicular inflammatory markers and apoptotic proteins (caspase-3 and Bax expression levels). In conclusion, combining 10-HDA and ZnO-NPs demonstrated synergistic potential in treating PbAc-induced testicular toxicity, thereby presenting a promising approach in nanomedicine and natural drugs.

Purpose: Non-alcoholic fatty liver disease is the most prevalent metabolic disorder that can lead to the development of non-alcoholic steatohepatitis (NASH) and, eventually, result in hepatocellular carcinoma. This study evaluated the therapeutic potential of berberine-loaded bovine serum albumin nanoparticles (BBR-BSA NPs) toward the induced NASH physical, biochemical, and ultrastructural changes. Methods: NASH was induced in male rats by an high-fat high-sucrose diet (HFHSD) and repeated carbon tetrachloride (CCl₄) injections. The treated groups received HFHSD/CCl₄ and were then administered BBR, BBR-BSA NPs, BSA NPs, and Atorvastatin for four weeks. Finally, physical, liver function, lipid profile, hepatic oxidative stress, and inflammatory biomarkers were determined. Furthermore, hepatic sigma 1 receptor (SIGMAR1) and autophagy signaling proteins were evaluated. The hepatic transmission electron microscopic and histopathological examinations were also assessed. Finally, the chemical- and protein–protein interaction networks were presented using the visualization tools STITCH 5.0 and STRING databases. In addition, molecular docking analyses were conducted to illustrate the binding of BBR and Atorvastatin toward SREBP-2 and mTOR targets. Results: The long-term administration of HFHSD/CCl₄ had the potential to develop a NASH model. This model is characterized by hepatic steatosis, necro-inflammation, and impaired endoplasmic reticulum-mitochondrial signaling. The results revealed an impaired SIGMAR1 and autophagy flux signaling pathways. In contrast, the administration of BBR-BSA NP improved the therapeutic properties of entrapped BBR on the alterations associated with NASH. The BBR-BSA NPs enhanced the autophagic flux and SIGMAR1 signaling modulators compared to BBR and Atorvastatin. The in-silico bioinformatics analysis demonstrated that BBR exhibited a more robust interaction with SREBP-2 and mTOR compared to Atorvastatin, which supports the in vivo results. Conclusion: BBR-BSA NPs restored hepatic homeostasis and enhanced the free BBR’s hepatoprotection against the induced NASH via the upregulation of SIGMAR1 and autophagy flux signaling.

The prolonged use of exogenous glucocorticoids, such as dexamethasone (Dex), is the most prevalent secondary cause of osteoporosis, known as glucocorticoid-induced osteoporosis (GIO). The current study examined the preventative and synergistic effect of aqueous chicory extract (ACE) and ethanolic purslane extract (EPE) on GIO compared with Alendronate (ALN). The phytochemical contents, elemental analysis, antioxidant scavenging activity, and ACE and EPE combination index were evaluated. Rats were randomly divided into control, ACE, EPE, and ACE/EPE MIX groups (100 mg/kg orally), Dex group (received 1.5 mg Dex/kg, Sc), and four treated groups received ACE, EPE, ACE/EPE MIX, and ALN with Dex. The bone mineral density and content, bone index, growth, turnover, and oxidative stress were measured. The molecular analysis of RANK/RANKL/OPG and Nrf2/HO-1 pathways were also evaluated. Dex causes osteoporosis by increasing oxidative stress, decreasing antioxidant markers, reducing bone growth markers (OPG and OCN), and increasing bone turnover and resorption markers (NFATc1, RANKL, ACP, ALP, IL-6, and TNF-α). In contrast, ACE, EPE, and ACE/EPE MIX showed a prophylactic effect against Dex-induced osteoporosis by modulating the measured parameters and the histopathological architecture. In conclusion, ACE/EPE MIX exerts a powerful synergistic effect against GIO by a mode of action different from ALN.

Ultraviolet C (UVC) devices are an effective means of disinfecting surfaces and protecting medical tools against various microbes, including coronavirus. Overexposure to UVC can induce oxidative stress, damage the genetic material, and harm biological systems. This study investigated the prophylactic efficacy of vitamin C and B12 against hepatotoxicity in UVC-intoxicated rats. Rats were irradiated with UVC (725.76, 967.68, and 1048.36 J/cm²) for 2 weeks. The rats were pretreated with the aforementioned antioxidants for two months before UVC irradiation. The prophylactic effect of vitamins against UVC hepatotoxicity was evaluated by monitoring the alteration of liver enzyme activities, antioxidant status, apoptotic and inflammatory markers, DNA fragmentation, and histological and ultrastructural alterations. Rats exposed to UVC showed a significant increase in liver enzymes, oxidant–antioxidant balance disruption, and increased hepatic inflammatory markers (TNF-α, IL-1β, iNOS, and IDO-1). Additionally, obvious over-expression of activated caspase-3 protein and DNA fragmentation were detected. Histological and ultrastructural examinations verified the biochemical findings. Co-treatment with vitamins ameliorated the deviated parameters to variable degrees. In conclusion, vitamin C could alleviate UVC-induced hepatotoxicity more than vitamin B12 by diminishing oxidative stress, inflammation, and DNA damage. This study could provide a reference for the clinical practice of vitamin C and B12 as radioprotective for workers in UVC disinfectant areas.

Blood–brain barrier (BBB) efflux transporters' overexpression hinders antiepileptic drug brain entry. Breast cancer resistance protein (BCRP) is a major BBB efflux transporter. In the present work, BCRP's role as a mechanism that might contribute to drug-resistant epilepsy (DRE) in a mouse model of acute seizures was studied with further assessment of the effect of its inhibition by ko143 and metformin (MET) on lamotrigine (LTG) bioavailability and efficacy. 42 male mice divided into 6 groups: G1: Normal control, G2: LTG-injected healthy mice: LTG 20 mg/kg i.p., G3: Acute seizures (A.S) mice: Pentylenetetrazole (PTZ) 50 mg/kg i.p., G4: LTG-treated A.S mice: LTG 20 mg/kg + PTZ 50 mg/kg i.p., G5: Ko143 + LTG treated A.S mice: Ko143 15 mg/kg i.p. before LTG + PTZ, G6: MET + LTG treated A.S mice: MET 200 mg/kg i.p. before LTG + PTZ. Seizures severity, serum, brain LTG, and brain BCRP were assessed. PTZ group experienced the highest seizure frequency and brain BCRP expression. Ko143 and MET groups showed a significant decrease in brain BCRP with subsequent improvement in brain LTG level and better seizure control. BCRP has a significant role in epilepsy resistance and its inhibition with ko143 or MET adds value to DRE management.