Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson's disease

Background This study was designed to investigate the neuroprotective effects of bromelain, which is known to have anti-oxidant and anti-inflammatory properties, against the neurotoxicity (induced by 6-OHDA) in SH-SY5Y cells. Methods and results To establish Parkinson's Disease (PD) model in cell culture conditions, SH-SY5Y cells were exposed to 200 mu M 6-OHDA for 1 day. Prior to 6-OHDA treatment, SH-SY5Y cells had been pre-treated with bromelain (25 mu g/mL, 50 mu g/mL, 75 mu g/mL and 100 mu g/mL). After 1 day, cell viability was determined with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assays. Oxidative stress was assessed with total antioxidant capacity (TAC), total oxidant status (TOS), glutathione reductase (GR) and malondialdehyde (MDA) analyses. The effect of the bromelain in SH-SY5Ycells was also examined by 4 ',6-diamidino-2-phenylindole (DAPI) staining. We found that 6-OHDA increased LDH leakage, and cellular apoptosis in SH-SY5Y cells. 6-OHDA aggravated oxidative stress by increasing TOS, MDA and GR and eventually promoted apoptosis in SH-SY5Y cells, while pretreatment with bromelain attenuated these toxic effects of 6-OHDA. Conclusions These findings indicated that bromelain, with its neuroprotective features can be useful for neuroprotection in PD

Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis

This study was designed to investigate the protective effects of Centella asiatica (CA) on cisplatin-induced hepatotoxicity and to clarify the underlying mechanism by biochemical, molecular, immunohistochemical, and histopathological analyses. Rats were pre-treated with two doses of CA (100 and 200 mg/kg, p.o.) for 14 consecutive days. Then, on the 15th day, hepatotoxicity was induced by a single cisplatin injection (10 mg/kg i.p.). On the 18th day, the rats were euthanized. CA effectively alleviated cisplatin-induced hepatic injury via reduction in AST, ALT, and ALP enzymes and a decrease in oxidative stress (decreased MDA and ROS, and increased SOD, CAT, and GSH). CA also mitigated the inflammatory damage by the inhibition of TNF-alpha, IL-1 beta, and NF-kappa B. The liver expression of caspase-3 and Bax was downregulated, while Bcl-2 was upregulated. Moreover, immunohistochemical results confirmed the recovery with CA by downregulation of iNOS and 8-OHdG expression. These results showed that with its antioxidant, anti-inflammatory, and anti-apoptotic activities, CA could help alleviate the hepatotoxic effects of cisplatin chemotherapy

Syringic acid protects against thioacetamide-induced hepatic encephalopathy: Behavioral, biochemical, and molecular evidence

The objective of this study was to elucidate the effects of syringic acid on thioacetamide-induced hepatic encephalopathy which is a complex serious syndrome with neuropsychiatric abnormalities related to acute liver dysfunctions like cirrhosis. Rats were treated with syringic acid (50 and 100 mg/kg, p.o.) for 14 days in treatment groups. Hepatic encephalopathy was induced by three doses of (200 mg/kg i.p.) thioacetamide injection. Syringic acid effectively alleviated thioacetamide-induced hepatic injury via reduction in ammonia, AST, ALT, ALP, LDH and decrease in oxidative stress (decreased MDA, ROS and increased SOD and GSH). Syringic acid also attenuated inflammatory injury by suppressing TNF-alpha, IL-1 beta, and NF-kappa B and increasing IL-10. The caspase-3 expression was also down-regulated in both liver and brain tissues. Immunohistochemical results confirmed the recovery with syringic acid by downregulation of iNOS, 8-OHdG and GFAP expression. Syringic acid decreased the deteriorating effects of thioacetamide as seen by reduced ammonia concentration and also preserved astrocyte and hepatocyte structure. The behavioral test results from elevated plus maze test, similar to the open-field locomotor test results, confirmed that syringic acid can reverse behavioral impairments. In conclusion, syringic acid exerted hepatoprotective and neuroprotective effects against hepatic encephalopathy by mitigating hepatotoxicity biomarkers, exerting antioxidant, anti-inflammatory effects in addition to suppressing hyperammonemia

Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation

The aim of this study was to investigate the molecular, biochemical, and histopathological effects of bromelain, which has antioxidant and anti-inflammatory properties, against cisplatin-induced ocular toxicity. The groups were designed as (1) Control, (2) Cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Bromelain (50 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Bromelain (100 mg/kg, orally for 14 consecutive days). The activity of total antioxidant capacity (TAC) and total oxidant status (TOS) and levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1 beta (IL-1 beta), IL-10, nuclear factor kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha) and 8-OHdG were measured in ocular tissue. The mRNA expression of NF-kappa B and Caspase-3 was also evaluated. Also, ocular sections were evaluated histopathologically. Bromelain demonstrated a dose-dependent protective effect in cisplatin-induced toxicity by regulating oxidative stress, inflammation, and tissue damage. Our results suggested that bromelain may be a potential adjuvant that can protect the eye from cisplatin-induced toxicity

Does Intravitreal Dopamine Agonist and Antagonist Administration Have Effects on the Brain? An Experimental Study in Rats

Objective: There might be dopaminergic connections between the retina and the brain. In this context, the study was aimed to investigate the possible interaction between the retina and basal ganglia through the dopaminergic system. Materials and Methods: In total, 32 healthy rats were randomized into 4 groups: healthy, Sham, dopamine antagonist injected group (risperidone, 0.04 mg/kg intravitreally), and dopamine agonist injected group (apomorphine, 0.4 mg/kg intravitreally). The locomotor activity and Morris water maze tests were applied to all rats twice, before the injection and 28 days after, to detect changes in movement, memory, and attention. Histopathologically, the basal ganglia and hippocampus regions were removed and examined. Results: In the locomotor activity test, a statistical significance was found between the first and last measurement values of the apomorphine group and a decrease in activities and an increase in resting times (P < .05). In the Morris water maze test, a statistical significance was detected between the first and last tests of the control group and the apomorphine groups and showed significantly shorter learning times (P < .05). Histological analyses of the substantia nigra and hippocampus were noteworthy in that the number of damaged neurons in the risperidone group was considerably higher than the other groups. The number of damaged neurons in the apomorphine group was significantly lower than in the healthy group. Conclusion: Intravitreal administration of dopamine agonists and antagonists has given rise to alterations in the cerebral dopaminergic system, leading to changes in locomotor activity and memory and histopathological changes

Achillea millefolium alleviates testicular damage in paclitaxel-intoxicated rats via attenuation of testicular oxido-inflammatory stress and apoptotic responses

The aim of this study was to investigate the effects of Achillea millefolium extract in paclitaxel-induced testicular toxicity in rats. The groups were designed as (1) control, (2) paclitaxel (8 mg/kg, intraperitoneally), (3) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (200 mg/kg, orally for 14 consecutive days) and (4) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Serum levels of testosterone, luteinising hormone and follicle-stimulating hormone, as well as total antioxidant capacity and total oxidant status were measured one day after receiving the last dose of Achillea millefolium extract. Testicular superoxide dismutase activity, malondialdehyde, tumour necrosis factor alpha and interleukin-1 beta levels, the expressions of nuclear factor kappa B and caspase-3 were evaluated. In addition, testicular sections were evaluated histopathologically and 8-hydroxy-2 '-deoxyguanosine was detected immunohistochemically. Achillea millefolium improved the levels of luteinising hormone, follicle-stimulating hormone and testosterone, upregulated testicular antioxidant enzymes and downregulated inflammation. Furthermore, we observed that Achillea millefolium restored testicular histopathological structure and significantly suppressed oxidative DNA damage and apoptosis by reducing the expression of caspase-3. Taken together, our results suggest that Achillea millefolium has protective effects against paclitaxel-induced testicular toxicity and is a promising natural product with the potential to improve male fertility

Assessment of the neuroprotective potential of d-cycloserine and l-serine in aluminum chloride-induced experimental models of Alzheimer’s disease:In vivo and in vitro studies

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain accompanied by synaptic dysfunction and neurodegeneration. No effective treatment has been found to slow the progression of the disease. Therapeutic studies using experimental animal models have therefore become very important. Therefore, this study aimed to investigate the possible neuroprotective effect of D-cycloserine and L-serine against aluminum chloride (AlCl(3))-induced AD in rats. Administration of AlCl(3) for 28 days caused oxidative stress and neurodegeneration compared to the control group. In addition, we found that aluminum decreases α-secretase activity while increasing β-secretase and γ-secretase activities by molecular genetic analysis. D-cycloserine and L-serine application resulted in an improvement in neurodegeneration and oxidative damage caused by aluminum toxicity. It is believed that the results of this study will contribute to the synthesis of new compounds with improved potential against AlCl(3)-induced neurodegeneration, cognitive impairment, and drug development research

A Selective Histamine H4 Receptor Antagonist, JNJ7777120, Role on glutamate Transporter Activity in Chronic Depression

Glutamate release and reuptake play a key role in the pathophysiology of depression. glutamatergic nerves in the hippocampus region are modulated by histaminergic afferents. Excessive accumulation of glutamate in the synaptic area causes degeneration of neuron cells. The H4 receptor is defined as the main immune system histamine receptor with a pro-inflammatory role. To understand the role of this receptor, the drug JNJ7777120 was used to reveal the chronic depression-glutamate relationship. We have important findings showing that the H4 antagonist increases the glutamate transporters’ instantaneous activity. In our experiment, it has been shown that blocking the H4 receptor leads to increased neuron cell viability and improvement in behavioral ability due to glutamate. Therefore, JNJ can be used to prevent neurotoxicity, inhibit membrane phospholipase activation and free radical formation, and minimize membrane disruption. In line with our findings, results have been obtained that indicate that JNJ will contribute to the effective prevention and treatment of depression