Understanding Cr(III) Action on Mitochondrial ATP Synthase and AMPK Efficacy: Insights from Previous Studies-a Review.

Chromium supplementation has been notably recognized for its potential health benefits, especially in enhancing insulin sensitivity and managing glucose metabolism. However, recent studies have begun to shed light on additional mechanisms of action for chromium, expanding our understanding beyond its classical effects on the insulin-signaling pathway. The beta subunit of mitochondrial ATP synthase is considered a novel site for Cr(III) action, influencing physiological effects apart from insulin signaling. The physiological effects of chromium supplementation have been extensively studied, particularly in its role in anti-oxidative efficacy and glucose metabolism. However, recent advancements have prompted a re-evaluation of chromium's mechanisms of action beyond the insulin signaling pathway. The discovery of the beta subunit of mitochondrial ATP synthase as a potential target for chromium action is discussed, emphasizing its crucial role in cellular energy production and metabolic regulation. A meticulous analysis of relevant studies that were earlier carried out could shed light on the relationship between chromium supplementation and mitochondrial ATP synthase. This review categorizes studies based on their primary investigations, encompassing areas such as muscle protein synthesis, glucose and lipid metabolism, and antioxidant properties. Findings from these studies are scrutinized to distinguish patterns aligning with the new hypothesis. Central to this exploration is the presentation of studies highlighting the physiological effects of chromium that extend beyond the insulin signaling pathway. Evaluating the various independent mechanisms of action that chromium impacts cellular energy metabolism and overall metabolic balance has become more important. In conclusion, this review is a paradigm shift in understanding chromium supplementation, paving the way for future investigations that leverage the intricate interplay between chromium and mitochondrial ATP synthase.

Maca modulates fat and liver energy metabolism markers insulin, IRS1, leptin, and SIRT1 in rats fed normal and high-fat diets.

Maca root extract on insulin, insulin receptor substrate-1 (IRS1), leptin, and NAD-dependent deacetylase sirtuin-1 (SIRT1), as well as body weight changes evaluated in this study for a 60 days model of normal and high-fat diet (HFD) fed rats. 28 male rats allocated to four groups: (i) Control, (ii) Maca (40 mg/kg/day), (iii) HFD, and (iv) HFD + Maca. After the 60 days of study, fat tissue and liver insulin levels decreased in the HFD and HFD + Maca groups in comparison to Control and Maca groups (p < .001). Maca group showed a significant IRS1 increase in the fat tissue (p < .0001). Leptin levels were the highest in the Maca group and the lowest in the HFD group in the fat tissue (p < .01). SIRT1 levels were found the highest in the Maca groups (p < .01). These results show the protective and regulatory effectiveness of Maca when fed with a normal or HFD diet.

Maca could improve endurance capacity possibly by increasing mitochondrial biogenesis pathways and antioxidant response in exercised rats.

The objective of this study was to shed light on the effect of a novel Lepidium peruvianum (Maca) blend on anti-fatigue capacities in exercised rats. Twenty-eight male albino rats were allocated into four groups (n = 7) at random: (i) Control (vehicle), (ii) Maca: (40 mg/kg/BW), (iii) WL-FST: weight-loaded forced swimming test group, and (iv) WL-FST + Maca group. Maca supplementation increased swimming time to exhaustion (p < .01), while decreased serum lactate and liver glycogen concentrations. Maca addition resulted in lower levels of serum, liver, and muscle MDA (p < .05). Muscle GPx activity increased in both Maca groups (p < .001). Moreover, NF-κB levels were less in the WL-FST + Maca compared to the WL-FST group (p < .001). Nrf1, Nrf2, PGC-1α, SIRT1, and TFAM levels were augmented in the WL-FST + Maca compared to the WL-FST (p < .05). Consequently, our Maca blend increased endurance capacity and prevented exercise-induced oxidative stress and lactic acid buildup. PRACTICAL APPLICATIONS: The brassica species Lepidium peruvianum (maca) has been consumed in Peru for centuries to enhance mood, libido, and energy. Although the positive effects of this plant on energy metabolism are accredited, the underlying molecular mechanisms of these effects have not been sufficiently elucidated. The current study's findings suggest that this innovative, exclusive maca powder blend can boost endurance while preventing oxidative stress and lactic acid buildup during acute exercise. The mechanism of this efficacy is thought to be caused by maca's regulatory properties on energy metabolism signaling receptors and strong antioxidant scavenging effects on the free radicals that are produced by prolonged exhaustive exercise periods.

Effects of maca (Lepidium meyenii) on nutrient digestibility and major nutrient transporters in rats fed a high-fat diet.

SCOPE: This study was carried out to investigate the efficacy of a new combination of root extracts of the Lepidium meyenii (maca) plant, known for its nutritional and energizing features as well as its antioxidant properties, on nutrient digestibility and nutrient transporters expression. METHODS AND RESULTS: A total of 28 Sprague-Dawley rats (8-week-old) were divided into four groups: (i) control, (ii) Lepidium m., (iii) high-fat diet (HFD), and (iv) HFD+Lepidium m. Maca was given to the rats as a powdered combination of the plant roots with a daily dose of 40 mg per kg BW. Maca administration significantly increased the digestibility of dry matter (DM), organic matter (OM), crude protein (CP), and ether extract (EE), and some nutrient transporter (Pept1/2, Fatp1, Glut1/2, and Sglt1)-expressions compared with non-treated control and HFD groups in the jejunum and ileum tissues (p < .0001). CONCLUSIONS: Maca supplementation improved the digestibility of nutrients and expressions of nutrient transporters in the small intestine of the rats. These results indicate the positive communication between maca consumption and nutrient absorption in the small intestines of the animals.

Allyl isothiocyanate attenuates LED light-induced retinal damage in rats: exploration for the potential molecular mechanisms.

PURPOSE: Environmental light pollution due to artificial light may increase the rate and severity of retinal diseases, and plant-based nutritional interventions with antioxidant properties have the potential to reverse this phenomenon. We aimed to investigate the potential effects of allyl isothiocyanate (AITC) against white light-emitting diode (LED)-induced retinal degeneration (RD) in the rats. METHODS: Twenty-eight male rats were allocated as: (i) Control, (ii) LED, (iii) LED + AITC (10 mg/kg BW), (iv) LED + AITC (20 mg/kg BW). Rats were administered with AITC for 28 days, followed by two days of intense environmental LED light (750 Lux) exposure to the eyes. Animals were sacrificed immediately at the end of the study, then the blood and eyeballs were taken for the biochemical, western blotting, and histopathology examinations. RESULTS: AITC lowered the serum and retina malondialdehyde (MDA) levels while significantly (p < 0.05) improving the retinal antioxidant enzyme activities in a dose-dependent manner. AITC improved retinal and outer nuclear layer (ONL) thickness as compared to the LED group (p < 0.05). AITC increased the levels of Bax, caspase-3, HO-1, GAP43, and VEGF, while decreasing IL-1ß, IL-6, NF-κB, Bcl-2, GFAP, Grp78, activating ATF4 and ATF6 as compared to the LED group (p < 0.05). CONCLUSION: In conclusion, four weeks of AITC administration to the rats showed specific protective effects against two days of intense LED light-induced retinal damage; through antiinflammatory, antioxidant, anti-apoptotic, and modulating mitochondrial metabolic pathways.

Different Doses of ß-Cryptoxanthin May Secure the Retina from Photooxidative Injury Resulted from Common LED Sources.

Retinal damage associated with loss of photoreceptors is a hallmark of eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Potent nutritional antioxidants were previously shown to abate the degenerative process in AMD. ß-Cryptoxanthin (BCX) is an essential dietary carotenoid with antioxidant, anti-inflammatory, and provitamin A activity. It is a potential candidate for developing intervention strategies to delay the development/progression of AMD. In the current study, the effect of a novel, highly purified BCX oral formulation on the rat retinal damage model was evaluated. Rats were fed with BCX for four weeks at the doses of 2 and 4 mg/kg body weight in the form of highly bioavailable oil suspension, followed by retinal damage by exposing to the bright light-emitting diode (LED) light (750 lux) for 48 hrs. Animals were sacrificed after 48 hours, and eyes and blood samples were collected and analyzed. BCX supplementations (2 and 4 mg/kg) showed improvements in the visual condition as demonstrated by histopathology of the retina and measured parameters such as total retinal thickness and outer nuclear layer thickness. BCX supplementation helped reduce the burden of oxidative stress as seen by decreased serum and retinal tissue levels of malondialdehyde (MDA) and restored the antioxidant enzyme activities in BCX groups. Further, BCX supplementation modulated inflammatory markers (IL-1ß, IL-6, and NF-κB), apoptotic proteins (Bax, Bcl-2, caspase 3), growth proteins and factors (GAP43, VEGF), glial and neuronal proteins (GFAP, NCAM), and heme oxygenase-1 (HO-1), along with the mitochondrial stress markers (ATF4, ATF6, Grp78, Grp94) in the rat retinal tissue. This study indicates that oral supplementation of BCX exerts a protective effect on light-induced retinal damage in the rats via reducing oxidative stress and inflammation, also protected against mitochondrial DNA damage and cellular death.

Effects of walnut oil on metabolic profile and transcription factors in rats fed high-carbohydrate-/-fat diets.

The aim of this study was to examine the effects of walnut oil (WO) on metabolic profile and transcription factors in rats fed high carbohydrate (HCD) and high-fat diet (HFD). Forty-two male rats were divided in to six groups: (a) Control, (b) WO (20 mg/kg BW), (c) HCD (20% of sucrose), (d) HCD + WO (e) HFD (42% of calories as fat), and (f) HFD + WO. HFD and HCD intake increased final body weights by 19% and 23% and visceral fat weights by 3- and 5-fold, respectively (p < .05 for all). In addition, serum glucose, total cholesterol, triglyceride, and free fatty acids (FFA) insulin, leptin, and MDA levels increased in rats fed with HFD and HCD. WO supplementation improved these metabolic parameters (p < .05 for all). HFD + WO and HCD + WO treated groups had a significant reduction in serum and liver malondialdehyde (MDA) levels by 12% or 15% (p < .05 for both). In addition, WO supplementation lowered the levels of hepatic nuclear factor kappa B (NF-κB) and NADPH oxidase subunit p22phox , whereas increased the endothelial-NO synthase (e-NOS), nuclear factor erythroid 2-related factor-2, and sirtuin-1 levels. In conclusion, WO supplementation could alleviate the adverse impacts of both HCD and HFD in the rats. PRACTICAL APPLICATIONS: This study suggests that WO intake can modulate carbohydrate metabolism and increase antioxidant capacity. These properties might be partially mediated through the regulation of the transcription factors and some proteins involved in energy metabolism, as well as a balance of oxidative stress, and insulin sensitivity.

Undenatured Type II Collagen (UC-II) in Joint Health and Disease: A Review on the Current Knowledge of Companion Animals.

OA is quite common in companion animals, especially in large breed dogs and horses. Collagen, the most abundant protein of mammals, has specific connective tissue types for skin, bones, reticulate, basal lamina, bones, cell surfaces, while type II collagen (UC-II) forms the main structure of cartilage tissue. Even at the smaller dosages, UC-II has also been reported to be more effective than the glucosamine and chondroitin sulfate supplements, which are the supplements most frequently used in the market. In this review, we summarize the effects of UC-II on joint health and function in health and disease conditions in companion animals.

Epigallocatechin 3-gallate attenuates arthritis by regulating Nrf2, HO-1, and cytokine levels in an experimental arthritis model.

Epigallocatechin 3-gallate (EGCG) is a polyphenol that has been shown to have antioxidant and anti-inflammatory effects. In this study, collagen-induced arthritis (CIA) model, in Wistar albino rats, was used to elucidate the effect of EGCG on pathogenetic pathways in inflammatory arthritis. The levels of serum TNF-α, IL-17, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx); the expression levels of tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); histopathologically, perisynovial inflammation and cartilage-bone destruction were examined. In the sham group, serum TNF-α, IL-17, and MDA levels increased, while SOD, CAT, GPx levels, and the expressions of Nrf2 and HO-1 decreased. On the other hand, in the EGCG administered groups, serum TNF-α, IL-17, and MDA levels improved, while SOD, CAT, GPx levels and the expressions of Nrf2 and HO-1 increased. Moreover, histopathological analysis has shown that perisynovial inflammation and cartilage-bone destruction decreased in the EGCG administered groups. These results suggest that EGCG has an antiarthritic effect by regulating the oxidative-antioxidant balance and cytokine levels in the CIA model, which is a surrogate experimental model of rheumatoid arthritis.

Lutein and zeaxanthin isomers may attenuate photo-oxidative retinal damage via modulation of G protein-coupled receptors and growth factors in rats.

BACKGROUND: Retina photoreceptor cells are specially adapted for functioning over comprehensive ambient light conditions. Lutein and Zeaxanthin isomers (L/Zi) can protect photoreceptor cells against excessive light degeneration. Efficacy of L/Zi has been assessed on some G protein-coupled receptors (GPCRs), transcription and neurotrophic factors in the retina of rats exposed to incremental intense light emitting diode (LED) illumination conditions. METHODS: Forty-two male rats (age: 8 weeks) were randomly assigned to six treatment groups, 7 rats each. The rats with a 3x2 factorial design were kept under 3 intense light conditions (12hL/12hD, 16hL/8hD, 24hL/0hD) and received two levels of L/Zi (0 or 100 mg/kg BW) for two months. Increased nuclear factor-kappa B (NF-κB), glial fibrillary acid protein (GFAP), and decreased Rhodopsin (Rho), Rod arrestin (Sag), G Protein Subunit Alpha Transducin1 (Gnat1), neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP43), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase 1 (HO-1) were observed in 24 h light intensity adaptation followed by 16 h IL and 8 h D. RESULTS: L/Zi administration significantly improved antioxidant capacity and retinal Rho, Rod-arrestin (Sag), Gnat1, NCAM, GAP43, BDNF, NGF, IGF1, Nrf2, and HO-1 levels. However, the levels of NF-κB and GFAP levels were decreased by administration of L/Zi. CONCLUSIONS: According to these results, L/Zi may be assumed as an adjunct therapy to prevent early photoreceptor cell degeneration and neutralize free radicals derived from oxidative stress.

Determining the insulin secretion potential for certain specific G-protein coupled receptors in MIN6 pancreatic beta cells

Background/aim: The polypeptide hormone insulin is essential for the maintenance of whole-body fuel homeostasis, and defects in insulin secretion and/or action are associated with the development of type 1 and type 2 diabetes. The aim of this study was to assess the role of some G-protein coupled receptors (GPCRs), GPR54, GPR56, and GPR75, and cannabinoid receptors CB1R and CB2R, in the regulation of pancreatic ß-cell function. Materials and methods: Insulin secretion from mouse insulinoma ß-cell line (MIN6) monolayers was assessed via insulin radioimmu-noassay (RIA). Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the expression of some specific GPCRs and the other receptors by MIN6 pancreatic ß-cells. Results: The agonists were not found to be toxic for the MIN6 pancreatic ß-cells within the range of the doses used in this study, whereas insulin secretion altered depending on the ligands and receptors. In addition, arachidonyl-2'-chloroethylamide (ACEA), carbachol, chemokine (C-C motif ) ligand-5 (CCL5), and exendin as well as phorbol myristate acetate (PMA) ligands showed significant increases in the insulin secretion of MIN6 pancreatic ß-cells. Conclusion: Understanding the normal ß-cell function and identifying the defects in ß-cell function that lead to the development of diabetes will generate new therapeutic targets

(3R, 3'R)-zeaxanthin protects the retina from photo-oxidative damage via modulating the inflammation and visual health molecular markers.

PURPOSE: Zeaxanthin protects the macula from ocular damage due to light or radiation by scavenging harmful reactive oxygen species. In the present study, zeaxanthin product (OmniXan®; OMX), derived from paprika pods (Capsicum annum; Family-Solanaceae), was tested for its efficacy in the rat retina against photooxidation. METHODS: Forty-two male 8-week-old Wistar rats exposed to 12L/12D, 16L/8D and 24L/0D hours of intense light conditions were orally administrated either 0 or 100 mg/kg BW of zeaxanthin concentration. Retinal morphology was analyzed by histopathology, and target gene expressions were detected with real-time polymerase chain reaction methods. RESULTS: OMX treatment significantly increased the serum zeaxanthin concentration (p < 0.001) and ameliorated oxidative damage by increasing the antioxidant enzyme activities in the retina induced by light (p < 0.001). OMX administration significantly upregulated the expression of genes, including Rhodopsin (Rho), Rod arrestin (SAG), Gα Transducin 1 (GNAT-1), neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP43), nuclear factor-(erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase (HO-1) and decreased the expression of nuclear factor-κB (NF- κB) and GFAP by OMX treatment rats. The histologic findings confirmed the antioxidant and gene expression data. CONCLUSIONS: This study suggests that OMX is a potent substance that can be used to protect photoreceptor cell degeneration in the retina exposed to intense light.

MAT, a Novel Polyherbal Aphrodisiac Formulation, Enhances Sexual Function and Nrf2/HO-1 Pathway While Reducing Oxidative Damage in Male Rats.

Mucuna pruriens, Ashwagandha, and Tribulus terrestris are known as the enhancers for sexual health, functional activities, vitality, and longevity. These herbs had been widely used in the Ayurveda medicine as aphrodisiacs through the ages, and their efficacy was also verified separately in our previous publication. Therefore, the aim of this study was to determine the effects of Mucuna, Ashwagandha, and Tribulus complexes on sexual function in rats. Twenty-eight male rats allocated to four groups as follows: (i) negative control (C); (ii) positive control or sildenafil citrate treated group (5 mg/kg) (S); (iii) MAT1 (combination of 10 mg Mucuna (M) + 10 mg Ashwagandha (A) + 10 mg Tribulus (T)/kg BW); (iv) MAT 2 (20 mg Mucuna + 20 mg Ashwagandha + 20 mg Tribulus/kg BW). There was no significant difference found between the MAT1 and MAT2 groups while they showed significantly increased testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels when compared to the negative control. Significant increases in Nrf2/HO1 levels and decreases in NF-κB were detected in MAT groups similar to the decrease in serum and testis malondialdehyde (MDA) levels as compared to both controls. The sperm motility, count, and rate also significantly improved in both MAT groups, while ALT, AST, creatinine, ALP, and urea levels did not change in any of the groups. Oral consumption of MATs combination in male rats resulted in inhibition of NF-κB and MDA and also increased sex hormones with Nrf2-mediated HO-1 induction. MAT combinations may improve sexual functions by increasing levels of sexual hormones and regulation of NF-κB and Nrf2/HO-1 signaling pathways.

Phytochemical Therapies in Vascular Functioning: A Molecular Approach.

There has been an increasing interest in the usage of natural products for the prevention and treatment of chronic diseases such as cardiovascular disease (CVD). Regular consumption of fruits, vegetables and whole grains has been shown to be negatively correlated with the risk of CVDs. These foods provide a diversity of nutrients and different bioactive compounds including phytochemicals, vitamins, minerals and fibers which play critical roles in the sustainability of optimal cardiovascular health. Plant-based foods or a nutritional cure are gradually being integrated into medical practice for CVD management partly due to the supporting experimental studies, clinical trials and epidemiological studies. These products have anti-oxidant, anti-inflammatory, hypoglycemic, hypolipidemic, hypotensive, anti-atherosclerotic, anti-thrombotic and hypocholesterolemic effects, depending on the dosage in cell and tissue cultures, animal models as well as in humans. The present review considers some novel ideas on some major phytochemicals which have been suggested to have protective and therapeutic potential in CVD. The data presented in this work have been compiled from studies that have mostly been carried out in recent years.

Comparative evaluation of the sexual functions and NF-κB and Nrf2 pathways of some aphrodisiac herbal extracts in male rats.

BACKGROUND: Mucuna pruriens, Tribulus terrestris and Ashwagandha (Withania somnifera) are widely known as antioxidant effective herbals and have been reported to possess aphrodisiac activities in traditional usages. In this study, we determined the effects of these herbals on sexual functions, serum biochemical parameters, oxidative stress and levels of NF-κB, Nrf2, and HO-1 in reproductive tissues. METHODS: Thirty-five male rats were divided into five groups: the control group, sildenafil-treated group (5 mg/kg/d), Mucuna, Tribulus and Ashwagandha groups. The extract groups were treated orally either with Mucuna, Tribulus or Ashwagandha (300 mg/kg b.w.) for 8 weeks. RESULTS: All of the extracts were found to be significantly effective in sexual functioning and antioxidant capacity and Tribulus showed the highest effectiveness. Serum testosterone levels significantly increased in Tribulus and Ashwagandha groups in comparison to control group. Tribulus was able to reduce the levels of NF-κB and increase the levels of Nrf2 and HO-1 to a much greater extent than Mucuna and Ashwagandha. CONCLUSIONS: These results demonstrate for the first time that Mucuna, Tribulus and Ashwagandha supplementation improves sexual function in male rats via activating Nrf2/ HO-1 pathway while inhibiting the NF-κB levels. Moreover, Tribulus terrestris extract was found to be more bioavailable from Ashwagandha extract followed by Mucuna extract. Schematic representation of the mode of action of some aphrodisiac herbal extracts to improve sexual functions.

Anti-diabetic potential of chromium histidinate in diabetic retinopathy rats.

BACKGROUND: Chromium (Cr) is commonly used as a complementary medicine for diabetes mellitus. Several studies suggest that Cr intakes may improve glucose metabolism and decrease oxidative stress. Therefore, we aimed to assess the effects of chromium histidinate (CrHis) supplementation using a range of reliable biomarkers of oxidative damage and histopathological changes in rats with diabetic retinopathy. METHODS: Diabetes was induced with streptozotocin [(STZ), 55 mg/kg] by intraperitoneal injection in male Long-Evans rats. Three weeks after STZ injection, rats were divided into four groups, namely, untreated normal controls, normal rats receiving CrHis (110 µg/kg/day); untreated diabetics and diabetics treated with CrHis (110 µg/kg/day) orally for 12 weeks. RESULTS: In the untreated diabetic group, levels of serum glucose, glycosylated haemoglobin (HbA1c), total cholesterol (TC) and retina malondialdehyde (MDA) were significantly increased, while expressions of retina insulin, and glucose transporter 1 (GLUT 1) and glucose transporter 3 (GLUT3) and level of serum insulin were decreased. CrHis supplementation was found to reduce the levels of glucose, HbA1c, total cholesterol and MDA and to improve the GLUT1, GLUT3 and insulin expressions in STZ-induced diabetic rats. CrHis prevents the changes in the expressions of GLUT1, GLUT3 and insulin and the level of MDA in the retina tissue, confirming the protective effect of CrHis supplementation against the retinopathy caused by STZ. Histopathologic findings suggest that the CrHis-treated diabetic group had normal retinal tissue appearance compared with the untreated diabetic group. CONCLUSIONS: These results verify that CrHis has critical beneficial effects against retinal complications. Although detailed studies are required for the evaluation of the exact mechanism of the ameliorative effects of CrHis against diabetic complications, these preliminary experimental findings demonstrate that CrHis exhibits antidiabetic effects in a rat model of diabetic retinopathy by regulating the glucose metabolism and suppressing retinal tissue damage.

Protective effects of resveratrol against streptozotocin-induced diabetes in rats by modulation of visfatin/sirtuin-1 pathway and glucose transporters.

This experiment was aimed at elucidating the protective effect of resveratrol against diabetes. Forty male Wistar albino rats were allocated into four groups: the control and streptozotocin (STZ)-induced diabetes groups were treated either with placebo (1 ml/kg, i.p.) or resveratrol (20 mg/kg, i.p.) for 8 weeks. Body weight, blood glucose and serum malondialdehyde (MDA) concentrations were monitored. At the end of the experimental period, expression levels of visfatin, sirtuin-1 (SIRT1) and glucose transporters (GLUTs, 2 and 4) were measured in skeletal muscle and pancreas by Western blotting. The resveratrol treatment partially compensated for body weight loss and alleviated hyperglycaemia and returned serum MDA concentrations to the control group levels. Data suggest that supplementation may reduce the severity of diabetes and its complications through suppressing oxidative stress and increasing potential to internalise glucose by extrahepatic tissues.

Comparative in vivo evaluations of curcumin and its analog difluorinated curcumin against cisplatin-induced nephrotoxicity.

Curcumin, a polyphenol, has pharmacological effects including antioxidant, anti-inflammatory and anti-cancer features. In this study, we have performed comparative in vivo evaluations of CDF (curcumin difluorinated) and curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) Control; (2) Cisplatin (7 mg/kg body wt, intraperitoneal as a single dose); (3) Cisplatin and CDF (50 mg/rat/day; for 12 days); (4) Cisplatin and curcumin (50 mg/rat/day), for 12 days). Cisplatin treated rats exhibited kidney injury manifested by increased serum N-urea and creatinine (P < 0.001). Kidney from cisplatin treated rats also exhibited significant increase in malondialdehyde (MDA) and 8-isoprostane levels (P < 0.001). Treatment with CDF and curcumin prevented the rise in serum N-urea, creatinine, MDA and 8-isoprostane as compared to experimental control group in kidney (P < 0.05). Compared to curcumin, CDF had greater potential in suppressing cisplatin-induced pro-inflammatory factors NF-κB and COX-2 as well as downstream markers Nrf2 and HO-1 (P < 0.05) in kidney. The analysis on anion transport markers (OAT1 and OAT3) showed a similar trend (CDF > curcumin). CDF could reduce the expression of multi-drug resistance markers OCT1, OCT2, MRP2 and MRP4 to a much greater extent than curcumin (P < 0.05). We also demonstrate that CDF influenced the expression of p-mTOR, p-p70S6K1, p-4E-BP1 and p-Akt. These data suggest that CDF can potentially be used to reduce the chemotherapy induced nephrotoxicity thereby enhancing the therapeutic window of cisplatin. The results also proved that compared to curcumin, CDF has superior protective effect in nephrotoxicity.

Chromium modulates expressions of neuronal plasticity markers and glial fibrillary acidic proteins in hypoglycemia-induced brain injury.

AIMS: This experiment investigated if chromium (Cr) as Cr-histidinate (CrHis) and Cr29 picolinate (CrPic) have a protective role in rats with hypoglycemia-induced brain injury, assessed by neuronal plasticity and regeneration potential. MAIN METHODS: Male Sprague-Dawley rats were prospectively divided into 2 groups: control and hypoglycemic (induced by insulin administration, 15U/kg, i.p., n=56). Hypoglycemic rats were then received randomly 1) none, 2) dextrose (on the day of sampling), 3) CrHis, or 4) CrPic. Cr-chelates were delivered via drinking water (providing 8µg elemental Cr per day) for one week prior to the hypoglycemia induction. The expressions of neuroplasticity markers [neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP-43), glial fibrillary acidic protein (GFAP)], glucose transporters (GLUT), and nuclear transcription proteins [nuclear factor-kappa (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and 4-hydroxyl nonenal (HNE)] were determined using Western blot. KEY FINDINGS: Hypoglycemia caused increases in the expressions of GLUT-1, GLUT-3, GFAP, NF-κB and HNE and decreases in the expression of NCAM's, GAP-43 and Nrf2 in the hippocampus, cerebellum, and cortex. Cr-chelates suppressed expressions of GLUTs, GFAP, NF-κB and HNE expressions and enhanced expressions of NCAM, GAP-43 and Nrf2, which were more notable for CrHis than for CrPic. SIGNIFICANCE: In conclusion, hypoglycemia leads to cerebral injury and Cr-chelates, particularly CrHis have protective and regeneration potential in cerebral tissues through modulating neuroplasticity markers and nuclear transcription proteins as well as facilitating glucose transporters.