👤 Ahmed Al-Emam

Pendimethalin (PMN) is a potent agrochemical that has shown severe neural alterations. Sanguinarine (SAN) is a naturally derived alkaloid that exhibits a wide range of biological properties. The current research was conducted to explore the palliative potential of SAN against PMN-induced neurotoxicity. Thirty-two Sprague Dawley rats were divided into the control, PMN (125 mg/kg), PMN (125 mg/kg) + SAN (15 mg/kg), and SAN (15 mg/kg) alone treated group. PMN intoxication upregulated the mRNA expressions of Aif1 (iba1), cd68, TNF-α, IL-10, IL-6, IL-1β, Nos2, Arg1, and Trem2 while inhibiting the mRNA expression of Tmem119. Neural tissues showed altered redox state after PMN exposure as evidenced by escalated levels of ROS and MDA coupled with marked declined in the activities of HO-1, GPx, CAT, GSR, SOD, and GST. Additionally, PMN administration provoked a sharp decline in the levels of NGF, BDNF, GDNF, Synaptophysin, and PSD-95. Moreover, exposure of PMN elevated the levels of Caspase-9, Bax, and Caspase-3 coupled with a significant reduction in the levels of Bcl-2. Neural tissues showed severe morphological alterations including vacuolar degeneration, neuronal loss, microglial activation, apoptotic bodies, capillary congestion, perineuronal vacuolation, and neural edema after PMN intoxication. Importantly, SAN supplementation notably alleviated neural damage via suppressing the activation of microglial and inflammatory pathways along with regulating redox profile, apoptotic indices, and histopathological alterations. Our in-silico assessment showed excellent binding affinity of SAN with key regulatory proteins thereby suggesting its critical role in suppressing the activation of microglial cells. Show less

(STL) is an extensively used anti-depressant drug that has been reported to induce organ damage including cardiac impairments. Nepetin (NEP) is a naturally derived flavonoid which exhibits excellent biological as well as pharmacological properties. This research investigation explored the cardioprotective ability of NEP to counter STL induced cardiotoxicity in Sprague Dawley rats. Thirty-six male Sprague Dawley rats were categorized into control, STL (20 mg/kg), STL (20 mg/kg) + NEP (10 mg/kg), and NEP (10 mg/kg) alone treated group. NEP intoxication significantly suppressed the expression of Notch 1, JAG1, DDL4, HES1, and HEY2 while escalating the levels of ROS and MDA. Besides, STL administration increased intraventricular septal thickness during IVSd and IVSs, promoted the internal diameter of left ventricular as well as elevated ESV as while reducing PWs and PWd, LVEF, and LVFS in echocardiographic examination. The enzymatic activities of HO-1, SOD, GPx, GSR, GST, CAT, and contents of GSH were reduced while the levels of CPK, ProBNP, troponin-T, CK-MB, LDH, C-reactive protein, BNP, and troponin-I were promoted after STL intoxication. Moreover, the levels of COX-2, IL-6, TNF-α, NF- κB, and IL-1β were elevated after STL exposure. Histopathological analysis showed abnormal cardiac architecture following the administration of STL. Importantly, NEP therapy significantly conferred cardio-protection via regulating redox state, reactivating Notch signaling, suppressing inflammatory responses, and improving histopathological alterations. Moreover, echocardiographic parameters were also found normal after NEP supplementation. These findings highlight the cardioprotective role of NEP in mitigating anti-depressant drugs induced cardiotoxicity. NEP confers cardio-protection against STL-induced cardiotoxicity via regulating oxidative stress, notch signaling, inflammation and cardiac function markers. These findings suggest this compound a promising therapy to mitigate anti-depressant drug-induced cardiac damage. Show less

Elaidic Acid (EA) is a major trans-fatty acid that has garnered significant attention due to its potential role in inducing systemic toxicity. The current investigation was conducted to assess the toxic effects of EA (50 mg/kg, 100 mg/kg, and 150 mg/kg) on testicular tissues of Sprague Dawley rats. EA intoxication disrupted Wnt/β-catenin via downregulating the expression of WNT3A and TCF7L2 while upregulating the expression of AXIN1 and GSK-3β. The activities of antioxidant enzymes were reduced while the levels of cellular oxidative stress were escalated following the EA exposure. EA administration disrupted the process of steroidogenesis as well as spermatogenesis through the downregulation of CYP11A1, 5α-reductase, 3β-HSD, CYP17A1, and StAR while elevating spermatogenic abnormalities in head, tail and neck of sperm cells. The levels of LH, androgen binding protein, FSH, inhibin B, plasma testosterone and estradiol were lowered after EA administration. Testicular tissues showed inflammatory responses after EA exposure that is evident by elevated levels of TNF-α, IL-1β, COX-2, IL-6 and NF-κB. The expressions of Bax and Caspase-3 were upsurged while expression of Bcl-2 was reduced following the EA intoxication. These findings showed EA exerted toxic effects on testicular tissues via elevating oxidative stress, inflammation and apoptosis. Show less