Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder that can affect brain health, primarily through the damaging effects of prolonged hyperglycemia. This condition increases oxidative s Show more
Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder that can affect brain health, primarily through the damaging effects of prolonged hyperglycemia. This condition increases oxidative stress (OS), neuroinflammation, and neuroapoptosis, ultimately impairing cognitive function. Acrylamide (ACY), a neurotoxicant formed during high-temperature food processing and present in cigarette smoke, may further aggravate these neurological disturbances. The present experiment examined the exacerbating effects of T2DM and ACY exposure on cognitive function, neurodegeneration, OS, neuroinflammation, and neuroapoptosis in diabetic rats. T2DM was induced via intraperitoneal injections of nicotinamide and streptozotocin, followed by daily oral doses of ACY for a month. Behavioral assessments (EPM, NOR, and Y-maze) evaluated cognitive performance. Brain tissues were analyzed for biochemical markers of neurodegeneration (GSK-3β, AChE, BACE1), OS (MDA, GSH, Catalase), neuroinflammation (NF-κB, TNF-α, PGE2, COX-2), and neuroapoptosis (Bcl-2, Bax, Caspase-3). Immunohistochemistry of Bcl-2, Bcl-6, CD138, and NF assessed structural brain changes. Results indicated that T2DM and ACY exposure significantly increased the incidence of neurological disturbances. Notably, through increased COX-2, PGE2, MDA, Bax, Bcl-6, Caspase-3, and cognitive decline deficits. This study highlights the harmful neurotoxic amplification of T2DM and ACY exposure, emphasizing the importance of public health measures to reduce ACY exposure through dietary and lifestyle changes, particularly among T2DM populations. Further research into neuroprotective strategies and underlying mechanisms is necessary. Show less
Tobacco consumption, a leading cause of over 8 million deaths annually, exposes individuals to acrylamide (ACY), a neurotoxin in cigarette smoke that disrupts neurotransmitter function and induces oxi Show more
Tobacco consumption, a leading cause of over 8 million deaths annually, exposes individuals to acrylamide (ACY), a neurotoxin in cigarette smoke that disrupts neurotransmitter function and induces oxidative stress, contributing to neurodegeneration. This study evaluated neuroprotective potential of montelukast (MTLU), a leukotriene receptor antagonist with anti-inflammatory and antioxidant properties, against ACY-induced neurotoxicity. Cognitive performance was assessed using elevated plus maze, novel object recognition, and Y-maze tests over 14 days. Biomarkers associated with neurodegeneration (BACE1, GSK-3β, AChE), neuroinflammation (COX-2, PGE2, TNF-α, NF-κB), oxidative stress (GSH, MDA, CAT), and apoptosis (Bcl-2, Caspase-3, Bax) were analyzed. Histopathological analyses of brain tissues were conducted to examine structural damage, and computational studies provided additional support for selected in vivo findings. MTLU significantly ameliorated ACY-induced cognitive deficits and reduced levels of GSK-3β, AChE, COX-2, PGE2, TNF-α, NF-κB, MDA, Bax, and Caspase-3 while enhancing antioxidant defenses (GSH) and upregulating Bcl-2. Histopathological analysis confirmed reduced structural brain damage, and molecular docking indicated strong binding potential for MTLU with AChE, COX-2, GSK-3β, BACE-1, and Caspase-3. While these findings suggest a protective role for MTLU in mitigating ACY-induced cognitive impairments, oxidative stress, neuroinflammation, and apoptosis, further research is needed to confirm its therapeutic potential and clinical relevance. Show less