Busulfan (BUS) is an anticancer agent with serious adverse effects on various body organs, including the lung and testis. Sitagliptin was proven to have antioxidant, anti-inflammatory, antifibrotic, and antiapoptotic effects. This study aims to evaluate whether sitagliptin, a DPP4I, ameliorates BUS-induced pulmonary and testicular injury in rats. Male Wistar rats were split into control, sitagliptin (10 mg/kg), BUS (30 mg/kg), and sitagliptin + BUS groups. Weight change, lung and testis indices, serum testosterone, sperm parameters, markers of oxidative stress [malondialdehyde (MDA) and reduced glutathione (GSH)], inflammation [tumor necrosis factor-alpha (TNF-α)], and relative expression of sirtuin1 (SIRT1) and forkhead box protein type O1 (FOXO1) genes were estimated. Histopathological examination of lung and testicular tissues was done to detect architectural changes [Hematoxylin & Eosin (H&E)], fibrosis (Masson’s trichrome), and apoptosis (caspase-3). Sitagliptin treatment reduced body weight loss, lung index, lung and testis MDA, serum TNF-α and sperm abnormal morphology, and increased testis index, lung and testis GSH, serum testosterone, sperm count, viability and motility. SIRT1/FOXO1 balance was restored. Also, sitagliptin attenuated fibrosis and apoptosis in lung and testicular tissues via reducing collagen deposition and caspase-3 expression. Accordingly, sitagliptin ameliorated BUS-induced pulmonary and testicular damage in rats via attenuating oxidative stress, inflammation, fibrosis, and apoptosis.

Aging-related sarcopenia is a degenerative loss of strength and skeletal muscle mass that impairs quality of life. Evaluating NUDT3 gene and myogenin expression as new diagnostic tools in sarcopenia. Also, comparing the concomitant treatment of resistance exercise (EX) and creatine monohydrate (CrM) versus single therapy by EX, coenzyme Q10 (CoQ10), and CrM using aged rats. Sixty male rats were equally divided into groups. The control group, aging group, EX-treated group, the CoQ10 group were administered (500 mg/kg) of CoQ10, the CrM group supplied (0.3 mg/kg of CrM), and a group of CrM concomitant with resistance exercise. Serum lipid profiles, certain antioxidant markers, electromyography (EMG), nudix hydrolase 3 (NUDT3) expression, creatine kinase (CK), and sarcopenic index markers were measured after 12 weeks. The gastrocnemius muscle was stained with hematoxylin–eosin (H&E) and myogenin. The EX-CrM combination showed significant improvement in serum lipid profile, antioxidant markers, EMG, NUDT3 gene, myogenin expression, CK, and sarcopenic index markers from other groups. The NUDT3 gene and myogenin expression have proven efficient as diagnostic tools for sarcopenia. Concomitant treatment of CrM and EX is preferable to individual therapy because it reduces inflammation, improves the lipid serum profile, promotes muscle regeneration, and thus has the potential to improve sarcopenia.

Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system associated with progressive neurodegeneration. Pirfenidone (Pir) is a well-known antifibrotic agent; however, Pir’s function in MS is little explored. We evaluated the neuroprotective effects of Pir in MS and its possible underlying mechanisms. Forty male Swiss mice were divided equally into control, cuprizone (CPZ), Pir, and CPZ + Pir groups. Assessment of motor function was conducted using neurobehavioral tests, EMG, and nerve conduction velocity (NCV). Mice’s brains were extracted to measure oxidative stress, neuroinflammatory markers, and the expression of neurotrophic genes. The corpus callosum and the sciatic nerve were subjected to histopathological and immunohistochemical studies. The CPZ group was associated with significant reductions in muscle power, frequency of contraction, sciatic NCV, SOD, IL-10, SIRT1, NGF, and neuregulin-1. Significant increases in MDA, TNF-α, INF-γ, IL-17, TGF-β, and NF-κB were also detected. Multiple areas of partially demyelinated nerve fibers in the corpus callosum, the loss of oligodendrocyte nuclei, and increased microglia and astrocytes were also observed. The sciatic nerve revealed partial demyelination with significantly reduced myelin basic protein (MBP) expression. Pir significantly restored motor function, demyelination, and neurodegenerative changes induced by CPZ. Besides the antifibrotic action of Pir, we concluded that it improves motor function in MS by alleviating the demyelinating process and neurodegeneration. Its potential anti-inflammatory, antioxidant, and antifibrotic properties could be contributing factors. These effects could be mediated by modulating the NF-κB, SIRT1, NGF, and neuregulin-1 pathways. Pir is a promising agent for treating MS.

Oxidative stress and neuroinflammation are crucial factors in the pathogenesis of Parkinson's disease (PD). Vitamin D (Vit D) and canagliflozin (CAN) are known to have anti-inflammatory and antioxidant properties. Together, they target key molecular pathways involved in PD, including oxidative stress and neuroinflammation, specifically, the small GTPase protein (RAC1)/nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which regulates brain's oxidative stress and inflammation. This study investigates the effects of Vit D and CAN alone and in combination in a rat model of PD. Fifty male Wistar rats were assigned to five groups (n = 10), including control, rotenone (ROT), Vit D + ROT, CAN + ROT, and Vit D + CAN + ROT. We assessed weight changes, brain weight, neurobehavioral functions, biochemical markers, and immunohistopathology of brain tissues. The results showed that Vit D treatment was more effective than CAN in alleviating PD symptoms, with the combination of Vit D and CAN offering the best therapeutic outcome. This combination therapy significantly improved serum Vit D, striatal dopamine (DA) levels, antioxidant status (reduced glutathione (GSH) and catalase (CAT), reduced oxidative stress (malondialdehyde (MDA)), and ameliorated inflammation (tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10)). Additionally, the combination therapy modulated the expression of RAC1, NF-κB, Nrf2, vitamin D receptors (VDR), and vitamin D-binding protein (DBP) and immunoexpression of tyrosine hydroxylase (TH), and α-synuclein (α-SYN). These findings suggest that Vit D and CAN synergistically modulate the RAC1/NF-κB/Nrf2 pathway, leading to improved neuroprotection in PD.

Hypertension (HTN) is a significant health issue with high morbidity, especially in the cardiovascular system, leading to mortality. HTN could be treated with exercise (Ex) and eugenol due to their antioxidant, anti-inflammatory, and antiapoptotic activities. 48 male Wistar rats (n = 8) were assigned to normal, deoxycorticosterone acetate (DOCA), losartan + DOCA, Ex + DOCA, eugenol + DOCA, and Ex + eugenol + DOCA groups. Blood pressure (BP), echocardiography, serum electrolytes, lipid profile, total antioxidant capacity (TAC), interleukin- 6 (IL- 6), endocan, endothelin- 1 (ET- 1), transforming growth factor-β1 (TGF-β1), plasma renin activity (PRA), and serum aldosterone were measured. PCR analyzed p38 mitogen-activated protein kinase (p38MAPK), c-Jun N-terminal kinases (JNK), and collagen 1 expression. Histopathology was used to evaluate heart and kidney tissues. Cardiac apoptosis was assessed using TUNEL staining. Losartan, aerobic Ex (30 min/day, 5 days/week), combined eugenol and Ex, and eugenol therapy mitigated systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic volume (LVEDV), serum sodium, IL- 6, endocan, ET- 1, TGF-β1, PRA, and serum aldosterone. These therapies attenuated histopathological changes, cardiac apoptosis, p38MAPK, JNK, and collagen 1. Conversely, ejection fraction (EF), serum potassium, and TAC levels were elevated compared to the DOCA group. Ex and eugenol monotherapy ameliorated DOCA-induced HTN in rats. Ex + eugenol combination showed equal efficacy to losartan in ameliorating DOCA-induced HTN, with better efficacy than Ex or eugenol alone. The combination’s antihypertensive effect may result from the synergistic/additive antioxidant, anti-inflammatory, and antiapoptotic effects of either therapy.

Objectives: to evaluate the potential antidepressant effect of rutin in diabetic rats and the assumed underlying mechanisms involved. Background: Depression is a common behavioral disorder among diabetic patients. Oxidative stress and inflammation are strongly involved in pathophysiology of diabetes induced depression. Rutin is major flavonoid that is proved to have neuroprotective effect through antioxidant and anti-inflammatory effects. Methods: Twenty four male Wistar rats were distributed (8/group) into control, diabetic and diabetic+Rutin groups. The depressive like behavior of the animals was conducted by forced swim test (FST). Fasting serum glucose, serum glycosylated hemoglobin A1c (Hb A1c), malondialdehyde (MDA), total antioxidant capacity, tumour necrosis factor-α (TNF-α), and interleukin 1β (IL-1β) were measured in addition, hippocampal serotonin and hippocampal BDNF were also assessed. Results: Diabetic group showed significant increase in fasting serum levels of glucose, HbA1c, MDA, TNF-α and IL-1β and significant decrease in serum total antioxidant capacity, hippocampal serotonin and hippocampal BDNF levels when compared to control group as well as increased immobility time and decrease latency to immobility of FST compared to control group. Rutin attenuated diabetes-induced depression through improving glycemic state, oxidative stress biomarkers, inflammatory mediators, and increased hippocampal serotonin and hippocampal BDNF levels. Conclusion: Rutin exerted antidepressant effect in diabetic rats via antioxidant, anti-inflammatory effects, and increased serotonin and BDNF levels.