Evaluating Motor Dysfunction and Oxidative Stress Induced by Trichloroethylene in Wistar Rats.

Trichloroethylene, a chlorinated solvent widely used as a degreasing agent, is a common environmental contaminant. Emerging evidence suggests that chronic exposure to trichloroethylene (TCE) contributes to the development of Parkinson's disease (PD). TCE induced LRRK2 kinase activity in the rat brain and produced a significant dopaminergic lesion in the nigrostriatal tract with elevated oxidative stress. Here we have utilized TCE-induced PD model for the assessment of test drug. Oral gavage administration of TCE at a dose of 1000 mg/kg/day for 6 weeks was utilized to induced PD. Muscle grip strength was estimated by rotarod and grid performance test. Motor activity by actophotometer and locomotor stability were assessed by forelimb locomotor scale (FLS) and forelimb step alternation test (FSAT). However, the postural stability was assessed by postural stability test (PST). Biochemical estimation consists of determination of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), GSH level (reduced glutathione), and nitrite concentration.

Apigenin protects melanocytes and improve tyrosinase activity in a hydroquinone induced vitiligo mouse model targeting P38 MAP kinase signaling: histopathology and immunohistochemistry analysis.

Apigenin (APG) is a plant-based flavonoid that possesses antioxidants, anti-inflammatory, and modulates P38 MAPK as well as tyrosinase. Hydroquinone (HQ), a phenolic compound was used to induce vitiligo in C57BL/6 mice. The present study was performed to check the therapeutic potential of apigenin in HQ-induced vitiligo via targeting P38 MAPK pathway. In the present study, 41 C57BL/6 mice were divided into six groups containing seven animals per group except normal group. (I) normal group, (II) HQ group, (III) to (IV) APG with (1%, 2.5%, 5%), and (VI) tacrolimus (TAC) group. Topical application of HQ was performed from day 1 to day 20 to, (II), (III) to (IV) APG with (1%, 2.5%, 5%), (VI) tacrolimus (TAC) group, and then APG; tacrolimus (TAC) was applied from day 21 to day 60 after removing the hair. In the case of (I) normal group and (II) HQ group, we smeared them with water for 60 days and HQ for 20 days in their individual group. On day 61 after anesthesia, a part of the target skin was peeled and blood serum was taken to check the level of malondialdehyde, cholinesterase, catalase, tyrosinase, pro-inflammatory cytokines, and expression of P38 MAPK, histology of melanin containing hair follicles and depigmentation evaluation. Applying HQ topically had a noticeable impact on depigmentation, inflammatory indicators, oxidative stress, and lowered tyrosinase activity. Further HQ reduced melanin containing hair follicles and increased expression of P38 MAPK was confirmed by histopathology and immunohistochemistry. Furthermore, application of APG and TAC after day 21 to 60 significantly reduced depigmentation, inflammatory markers, oxidative stress, and increased tyrosinase. Furthermore, APG increased melanin containing hair follicles and decreased expression of non-phosphorylated P38 MAPK, as confirmed by histopathology and immunohistochemistry. Our finding demonstrated that APG significantly prevented HQ-induced vitiligo by acting as an anti-inflammatory, increasing tyrosine, and reducing the expression of non-phosphorylated P38 MAPK.

Pharmacological approach using doxycycline and tocopherol in rotenone induced oxidative stress, neuroinflammation and Parkinson's like symptoms.

BACKGROUND: Parkinson's disease (PD) is a second most common neurodegenerative disorder characterized by the selective and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta. Rotenone is a neurotoxin which selectively degenerate dopaminergic neurons in striatum, leading to cause PD like symptoms. METHOD: Rotenone was administered at a dose of 1.5 mg/kg, i.p. from day 1 to day 40. Treatment with doxycycline (50 and 100 mg/kg, p.o), tocopherol (5 mg and 10 mg/kg, p.o) alone, doxycycline (50 mg/kg, p.o) in combination with tocopherol (10 mg/kg, p.o), and ropinirole (0.5 mg/kg, i.p.) was given for 40 days 1 h prior to administration of rotenone. All behavioral parameters were analyzed on weekly basis. On day 41, animals were sacrificed and the striatum region was isolated for neurotransmitters estimation (dopamine, serotonin, norepinephrine, GABA and glutamate), biochemical analysis (GSH, nitrite, LPO, mitochondrial complexes I and IV), inflammatory markers estimation (IL-6, IL-1ß and TNF-α) and activity of MAO-A, MAO-B. RESULT: Doxycycline and tocopherol in combination significantly attenuated behavioral, neurotransmitters and biochemical alterations induced by rotenone in experimental rats as compared to alone treatment with DOX and TOCO. Similarly, DOX and TOCO combination significantly reduced the level of inflammatory markers, prevented the biochemical changes, decreased MAO-A and MAO-B and improved complex-I, complex-IV, cAMP levels significantly. CONCLUSION: The current study revealed that a combination of doxycycline with tocopherol contributed to the prevention of PD like symptoms in rats by antioxidant, anti-inflammatory, MAO inhibitory and neuromodulatory mechanisms.