Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycetes), Mycelia Attenuates Doxorubicin-Induced Oxidative Stress and Upregulates Krebs Cycle Dehydrogenases Activity and ATP Level in Rat Brain.

Post-chemotherapy-induced cognitive dysfunction remains one of the challenges in cancer survivors. Cytokine-induced neurotoxicity manifests in subjects at any time after doxorubicin (DOX) chemotherapy. We examined the effect of bioactive Cordyceps militaris mycelia extract (CM) on the energy status, oxidative stress, and acetylcholinesterase activity in the brain of DOX treated rats. The CM (150 and 300 mg/kg b.w.) and DL-α lipoic acid (LA, 100 mg/kg b.w) were administered orally once daily for 5 days to male Wistar rats prior to the DOX administration (18 mg/kg as 3 doses of 6 mg/kg, i.p. b.w.) and continued for 6 more days. Cellular antioxidant status, Krebs cycle dehydrogenases, electron transport chain complexes (ETC) (I, III, and IV), adenosine triphosphate (ATP) level, advanced oxidation of protein products (AOPP), and acetylcholinesterase (AchE) activities were determined in the brain homogenate. The DOX alone treated group of animals showed significant decrease (p < 0.05) of brain antioxidant levels, Krebs cycle dehydrogenases activities, ETC complex activities, and decreased ATP level, while lipid peroxidation and AOPP levels were elevated. CM at 300 mg/kg b.w. or LA at 100 mg/kg b.w. elevated antioxidant status, Krebs cycle dehydrogenases, and complex activities and thus alleviated the toxicity. CM also inhibited the AchE activity in brain. The experimental results thus reveal that CM possessed excellent capacity to attenuate oxidative stress, upregulate respiratory chain complex activity and ATP levels, as well as inhibition of AchE activity.

Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Prevents Doxorubicin-Induced Cardiotoxicity in Rats.

Doxorubicin (DOX) is an anticancer drug used extensively to treat a variety of human malignancies. DOX chemotherapy often leads to serious cardiotoxicity. We examined the ability of a Ganoderma lucidum extract (GLE) to prevent DOX-associated cardiotoxicity. DOX treatment of cardiac tissue drastically increased levels of creatine kinase (CK), lactate dehydrogenase (LDH), lipid peroxidation (thiobarbituric acid-reactive substances), advanced oxidation protein products (AOPPs), and protein carbonyls (PCOs), and significantly decreased reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities. Administration of GLE restored CK, LDH, AOPPs, and PCOs to almost normal levels and significantly enhanced the activity of SOD, GPx, catalase, and GSH; it also downregulated lipid peroxidation. Histopathological observations, hematology profiles, and electrocardiography parameters supported the protective effect of GLE against cardiotoxicity associated with DOX treatment.

A Recent Update on the Effects of Omega-3 Fatty Acids in Alzheimer's Disease.

Dietary long chain polyunsaturated fatty acids belong to omega (ω)-3, -6 or -9 series. Both experimental and clinical studies demonstrated the beneficial effect of ω -3 fatty acids of fish oil, Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) against human ailments including cardiovascular diseases and rheumatoid arthritis. They are metabolized in cyclooxygenase and lipooxygenase pathways and also by cytochrome P450 isozymes. Biological importance of DHA in the development of brain and retina are well established. Recent studies highlighted the beneficial effect of ω-3 fatty acids in Alzheimer's Disease (AD) which may be attributed to their antioxidant, anti-inflammatory, antiapoptotic and neurotrophic properties. The effect was obtained by the consumption of either individual or combination of ω -3 fatty acids. The anti-inflammatory effect can be ascribed to the decreased cytokines and monocytic chemotactic protein-1 level by suppressing the nuclear factor-kappa B. Further, they inhibit cyclooxygenase-2 and nitric oxide synthase-2 activities. The antiapoptotic activity is due to the lowered Bax/Bcl ratio or caspase 3 levels. They can induce the transcription factor, nuclear erythroid factor-2 mediated expression of superoxide dismutase- 2 in order to facilitate the antioxidant effect. Both DHA and EPA can enhance the nerve growth factor level. Overall, they are beneficial to improve the cognitive function in very mild AD and major depressive disorder. Despite the beneficial effects, ω-3 fatty acids are easily prone to peroxidation. This review article discusses the recent update on the roles of ω -3 fatty acids in AD.

Zingiber officinale Roscoe ameliorates anticancer antibiotic doxorubicin-induced acute cardiotoxicity in rat.

Oxidative stress (OS) has been suggested in the cardiotoxicity induced by anticancer antibiotic doxorubicin (DXN). The cardioprotective effects of aqueous ethanol extract of Zingiber officinale was evaluated against DXN-induced acute cardiac damage in rat. The results of the study demonstrated that Z. officinale significantly and dose dependently protected the cardiotoxicity induced by DXN. The activities of serum glutamate oxaloacetate transaminase and serum lactate dehydrogenase activity in the DXN alone treated group of animals were significantly (p<0.01) elevated when compared to normal animals. The activities were reduced in the Z. officinale (200 and 400 mg/kg, p.o) plus DXN treated groups. The cardiac malondialdehyde was elevated in the DXN alone treated group and declined significantly in the Z. officinale (400 mg/kg) plus DXN treated group. The results concluded that aqueous ethanol extract of Z. officinale ameliorated DXN-induced cardiotoxicity. The protection can be ascribed to the free radical scavenging activity of Z. officinale. This protective effect may suggest the adjuvant role of Z. officinale against OS induced by cancer chemotherapeutants, which warrant further research.

Homocysteine in ocular diseases.

Homocysteine (Hcy) is a derived sulfur-containing and non-proteinogenic amino acid. The metabolism of Hcy occurs either through the remethylation to methionine or transsulfuration to cysteine. Studies have identified hyperhomocysteinemia (HHcy) as one of the possible risk factors for a multitude of diseases including vascular, neurodegenerative and ocular diseases. Association of HHcy with eye diseases such as retinopathy, pseudoexfoliative glaucoma maculopathy, cataract, optic atrophy and retinal vessel atherosclerosis is established. The molecular mechanism underlying these ocular diseases has been reported as impaired vascular endothelial function, apoptosis of retinal ganglion cells, extracellular matrix alterations, decreased lysyl oxidase activity and oxidative stress. The formed homocysteine-thiolactone in HHcy has stronger cytotoxicity and pro-inflammatory properties which can induce lens opacification and optic nerve damage. The metabolism of Hcy requires enzymes with vitamins such as folic acid, vitamins B12 and B6. Despite the mixed conclusion of various studies regarding the level of these vitamins in elder people, studies recommended the treatment with folate and B12 to reduce Hcy levels in subjects with or without any defect in the enzymes involved in its metabolism. The levels of Hcy, folate, B6 as well as B12 should be measured early in patients with visual impairment that would aid to screen patients for life-threatening disorders related with HHcy. Elder patients may supplement with these vitamins in order to attenuate the ocular damages. This article discusses the association of Hcy in ocular diseases and the possible mechanism in the pathogenesis.

Effect of palladium α-lipoic acid complex on energy in the brain mitochondria of aged rats.

CONTEXT: According to the mitochondrial mutation theory of aging, the impairment of mitochondrial functions and decline of cellular bioenergetics are induced by highly reactive oxygen species (ROS). Supplementation with antioxidants may protect mitochondria against respiration-linked oxidative stress and reduce decay by preserving genomic and structural integrity. Several clinical studies have reported beneficial effects of α-lipoic acid (LA) administration in individuals with Alzheimer's disease, particularly improving their spatial orientation; however, no studies have been reported on the effects of palladium α-lipoic acid (Pd-LA). OBJECTIVE: The current study examined the effects of the Pd-LA complex on mitochondrial energy status in the brains of aged rats. DESIGN: The study used male Wistar rats, some that were older than 24 mo and weighed approximately 350 ± 50 g and some that were younger than 24 mo and weighed approximately 175 ± 25 g. The research team divided the rats into 5 groups of 6 rats. SETTING: The study was conducted at the Amala Cancer Research Centre in Amala Nagar, Thrissur, Kerala, India. INTERVENTION: Three groups of rats were controls: (1) young controls administered no solution, (2) aged controls administered 1 mL/kg of a 0.25% solution (PO) of sodium hydroxide (NaOH), and (3) positive aged controls treated with LA (7.6 mg/kg, PO) dissolved in an alkaline saline (0.25% NaOH, w/v). Two groups were intervention groups: (1) aged rats treated with 1.2 mg/kg of Pd-LA (PO) and (2) aged rats treated with 23.5 mg/kg of Pd-LA (PO). The research team administered the solutions once daily for 30 d. After 30 d, all animals were sacrificed. OUTCOME MEASURES: The research team evaluated serum transaminases, lactate dehydrogenase (LDH), serum urea, and creatinine. The activities of superoxide dismutase (SOD), catalase (CAT), and the levels of reduced glutathione (GSH) were determined in the blood samples. Krebs cycle dehydrogenases were evaluated in the brain mitochondria. Furthermore, the activities of the respiratory chain complexes I, III and IV as well as adenosine triphosphate (ATP) levels were estimated in the mitochondrial fraction. RESULTS: The study found that Pd-LA elevated the mitochondrial ATP levels in the brains of aged rats by enhancing the activity of not only the Krebs cycle dehydrogenases but also complexes I and IV. Furthermore, Pd-LA improved the body weight and blood antioxidant status of aged rats without affecting the functions of liver or renal cells. CONCLUSIONS: The results of the current study demonstrate that Pd-LA improves mitochondrial energy status in the brains of aged rats. The effects can be attributed to the enhancing effect on the Krebs cycle dehydrogenase and the activities of complexes I, III, and IV. The results further support the possible use of Pd-LA as an adjuvant treatment, together with the standard cholinesterase inhibitors, in individuals with mild or moderate dementia caused by Alzheimer's disease (AD).

Phellinus rimosus (Berk.) pilat attenuates 7,12-dimethylbenz[a] anthracene induced and croton oil promoted skin papilloma formation in mice.

The roles of 7,12-dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), and 12-O-tetradecanoylphorbol-13-acetate (TPA) a skin tumor promoter present in croton oil, are clearly implicated in the formation of skin papilloma. The effect of ethyl acetate extract of Phellinus rimosus, a polypore macro fungus, against croton oil-induced skin inflammation, lipid peroxidation and tumor promotion was studied. The antiinflammatory and lipid peroxidation inhibiting activities were determined by topical application of extract of P. rimosus (10 and 20 mg) prior to the application of 0.1 ml of 50% croton oil in acetone. The tumor promotion inhibiting effect of P. rimosus was evaluated against DMBA-initiated, croton oil promoted two-stage carcinogenesis model in mouse skin. The results showed that topical application of the extract (10 and 20 mg) significantly (p < 0.01) and dose dependently attenuate the inflammatory edema as well as lipid peroxidation induced by croton oil. Similarly, topical application of extract (1 and 5 mg) effectively ameliorated the croton oil promoted skin papilloma formation. The results of this study concluded that ethyl acetate extract of P. rimosus showed antitumor activity against DMBA initiated, croton oil promoted skin papilloma formation which can be partially ascribed to the antiperoxidative and anti-inflammatory effects of the extract.