Co-administration Of Ascorbic Acid Research Articles

Antioxidant-induced modulation of sympathetic transduction to arterial blood pressure in humans

Purpose: Excess plasma free fatty acids (FAA) promote oxidative stress and an increase in peripheral resistance. Therefore, we tested the hypothesis that excess FAA limits sympathetic control of arterial blood pressure (BP) and that sympathetic control would be restored during co-administration of ascorbic acid, which is an antioxidant with vasodilatory properties. Methods: A 20% IV fat emulsion (Intralipid) was administered for 2 hours to 5 lean, healthy adults with and without co-infusion of ascorbic acid (separate visits) in a double-blinded, crossover study design. Sympathetic control of BP was examined by determining the BP response to individual bursts of muscle sympathetic nerve activity (MSNA) (microneurography). Briefly, beat-to-beat mean arterial pressure (MAP) was measured continuously (finger cuff) and signal-averaged over 15 cardiac cycles following each detected burst of MSNA over a 10-min resting period. Results: In contrast to our hypothesis, no change was observed in sympathetic transduction during lipid infusion (1.5 ± 0.4 vs. 1.4 ± 3 mmHg, P=0.75). However, co-infusion of ascorbic acid significantly increased sympathetic transduction compared with baseline (1.5 ± 0.4 vs. 2.0 ± 3 mmHg, P=0.04), in addition to reducing peripheral resistance (0.73 ± 0.11 vs. 0.53 ± 12 mmHg·min·mL−1, P=0.07). MSNA and MAP were not significantly changed during the 2-hr infusions. Conclusions: These preliminary findings suggest that excess FAA do not modulate sympathetic transduction in lean, healthy adults. However, ascorbic acid infusion reduces peripheral resistance and increases sympathetic transduction, demonstrating an inverse relation between peripheral resistance and sympathetic transduction in healthy adults. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366) The contents are solely the responsibility of the authors and do not necessarily represent the offcial views of the NIH or NCATS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ascorbate and Alpha-Tocopherol Mitigate Toxic Pathological Changes in Adult Wistar Rats Exposed to Cypermethrin

Excessive and uncontrolled use of pyrethroids such as cypermethrin (CYP) for pest control in Nigeria can adversely affect humans. This study investigated the oxidative stress response to cypermethrin exposure as well as the therapeutic effect of ascorbate and alpha-tocopherol when administered singly or co-administered. Additionally, the lungs and heart of the exposed animals were histologically assessed for cypermethrin-induced cytopathic changes. Twenty-five adult male Wistar rats weighing between 180 – 200g were randomly assigned to five groups of five animals each. Group I was the unexposed control group, while Group II was the exposed untreated group that was orally administered Cypermethrin at a dose of 10mg/kg/bw. Group III – V was given cypermethrin at standard doses of 10mg/kg/bw, and orally administered with ascorbate (5000mg/kg/bw), alpha-tocopherol (3000mg/kg/bw) and co-administration of ascorbate and alpha-tocopherol (5000mg/kg/bw and 3000mg/kg/bw) respectively. Animals were euthanized after 28 days, and samples were processed for histological and biochemical studies. The results showed elevated malondialdehyde (MDA) levels with a concurrent marked decrease in superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities (p<0.05) in the cypermethrin-exposed untreated rats, while histopathological findings revealed inflammation and congestion in the organs studied. The co-administrative treatment with ascorbate and alpha-tocopherol better restores biochemical parameters than their single administration. Conclusively, co-administration of ascorbic acid and alpha-tocopherol ameliorates cypermethrin-induced oxidative damage better than single administration, which may be due to their synergistic antioxidant properties.

Polymerized human cord hemoglobin assisted with ascorbic acid as a red blood cell substitute alleviating oxidative stress for blood transfusion.

Introduction: Blood transfusion is widely used in clinical settings, where considerable efforts have been devoted to develop red blood cell substitutes to overcome blood shortage and safety concerns. Among the several kinds of artificial oxygen carriers, hemoglobin-based oxygen carriers are promising due to their inherent good oxygen-binding and -loading properties. However, difficulties in prone to oxidation, production of oxidative stress, and injury in organs limited their clinical utility. In this work, we report a red blood cell substitute composed of polymerized human cord hemoglobin (PolyCHb) assisted with ascorbic acid (AA) that alleviates oxidative stress for blood transfusion. Methods: In this study, the in vitro impacts of AA on the PolyCHb were evaluated by testing the circular dichroism, methemoglobin (MetHb) contents and oxygen binding affinity before and after the addition of AA. In the in vivo study, guinea pigs were subjected to a 50% exchange transfusion with PolyCHb and AA co-administration, followed by the collection of blood, urine, and kidney samples. The hemoglobin contents of the urine samples were analyzed, and histopathologic changes, lipid peroxidation, DNA peroxidation, and heme catabolic markers in the kidneys were evaluated. Results: After treating with AA, there was no effect on the secondary structure and oxygen binding affinity of the PolyCHb, while the MetHb content was kept at 55%, which was much lower than that without AA treating. Moreover, the reduction of PolyCHbFe3+ was significantly promoted, and the content of MetHb could be reduced from 100% to 51% within 3h. In vivo study results showed that PolyCHb assisted with AA inhibited the formation of hemoglobinuria, upgraded the total antioxidant capacity and downgraded the superoxide dismutase activity of kidney tissue, and lowered the expression of biomarkers for oxidative stress, e.g., malondialdehyde (ET vs ET+AA: 4.03±0.26μmol/mg vs 1.83±0.16μmol/mg), 4-hydroxy-2-nonenal (ET vs ET+AA: 0.98±0.07 vs 0.57±0.04), 8-hydroxy 2 deoxyguanosine(ET vs ET+AA: 14.81±1.58ng/ml vs 10.91±1.36ng/ml), heme oxygenase 1 (ET vs ET+AA: 1.51±0.08 vs 1.18±0.05) and ferritin (ET vs ET+AA: 1.75±0.09 vs 1.32±0.04). The kidney histopathology results also demonstrated that kidney tissue damage was effectively alleviated. Conclusion: In conclusion, these comprehensive results provide evidence for the potential role of AA in controlling oxidative stress and organ injury in the kidneys induced by PolyCHb, and suggest that PolyCHb assisted with AA has promising application for blood transfusion.

Ascorbic acid co-administration with a low dose of diminazene aceturate inhibits the in vitro growth of Theileria equi, and the in vivo growth of Babesia microti.

In the current investigation, the effect of ascorbic acid on the in vitro growth of several piroplasm including Babesia bovis (Bartonella bovis), Baconia bigemina, B. caballi, and Theileria equi (T. equi), as well as against Brucella microti in mice was assessed. The antipiroplasm efficacy of ascorbic acid in vitro and in vivo was assessed using a fluorescence-based SYBR Green I test. Using atom pair fingerprint (APfp), we investigated the structural similarity between ascorbic acid and the commonly used antibabesial medicines, diminazene aceturate (DA) and imidocarb dipropionate (ID). In vitro cultures of B. bovis and T. equi were utilized to determine the ascorbic acid and DA interaction using the Chou-Talalay method. Ascorbic acid inhibited B. bovis, B. bigemina, T. equi, and B. caballi growth in vitro in a dose-dependent manner. The APfp results revealed that ascorbic acid and DA have a maximum structural similarity (MSS). On a T. equi culture in vitro, ascorbic acid showed a synergistic interaction with DA, with a combination index of 0.28. B. microti growth was decreased by 41% in vivo using ascorbic acid combined with a very low dosage of DA (6.25mgkg-1). The results imply that ascorbic acid /DA could be a viable combination therapy for the treatment of T. equi and that it could be utilized to overcome the resistance of Babesia parasites to full doses of the regularly used antibabesial medication, DA.

ROLE OF ASCORBIC ACID ON ALTERED LEVELS OF TESTOSTERONE DURING CHEMOTHERAPY

Background: Improvement in quality of life of cancer survivors has become a significant healthcare dilemma. Despite having important part in the support of spermatogenesis, few studies are conducted on Leydig cells secretion, i.e., testosterone which has an important role in fertility The objective of this study was to demonstrate altered serum testosterone levels by anthracycline on mice and to study changes observed in serum level in DOX affected mice with co-administration of antioxidant ascorbic acid. Methodology: Male mice aged five weeks were used. The animals were divided into 3 groups of 10 mice each. Animals in Group A were given normal saline intraperitoneally (IP). Group B mice were given DOX IP alone. In Group C, DOX and ascorbic acid were given orally. Blood samples were taken through cardiac puncture. Sera from centrifuged blood were tested for testosterone using ELISA kit. Results: Serum testosterone levels were 1.61±1.77, 6.22±4.78, and 1.98±0.45 ng /ml in Group A, B and C respectively. The administration of DOX induced significant increase (p<0.001) in the serum testosterone level. However co-administration of Ascorbic acid with DOX significantly reduced (p<0.001) the serum testosterone level. Conclusion: Ascorbic acid has a role against DOX induced altered hormonal levels. Pak J Physiol 2022;18(2):3?5

Impact of ascorbic acid in reducing the incidence of vancomycin associated nephrotoxicity in critically ill patients: A preliminary randomized controlled trial

Background Antioxidants show nephroprotective effect against vancomycin associated nephrotoxicity (VAN) in animals. This study aimed to assess the ascorbic acid nephro-protective role against VAN clinically.Methods Forty-one critically ill patients were randomly assigned to one of two groups: intervention group (vancomycin IV plus ascorbic acid, n=21) or control group (vancomycin IV only, n=20). Primary outcomes were the incidence of VAN and the absolute change in creatinine parameters, while mortality rate was the secondary outcome. Nephrotoxicity was defined as an increase in serum creatinine (S.cr) by at least 0.5 mg/dL or 50% of baseline for at least two successive measurements. This study is registered at Clinicaltrials.gov (NCT03921099), April 2019.Results Mean absolute S.cr increase was significant when compared between both groups, P-value = 0.036, where S.cr increased by 0.05(0.12) and 0.34(0.55) mg/dL in the intervention and control groups, respectively. Mean absolute Cr.cl decline was significant when compared between both groups, P-value = 0.04, where Cr.cl was decreased by 5.9(17.8) and 22.3(30.4) ml/min in the intervention and control groups, respectively. Incidence of VAN was 1/21(4.7%) versus 5/20(25%) in the intervention and control groups, respectively (RR: 0.19; CI: 0.024–1.49; P-value = 0.093). Mortality was higher in the control group; however, it was not statistically significant, P-value = 0.141.Conclusion Co-administration of ascorbic acid with vancomycin preserved renal function and reduced the absolute risk of VAN by 20.3%, however, the reduction in VAN incidence didn’t reach statistical significance level. Further large multicenter prospective trials are recommended.

Impact ofascorbic acidinreducingthe incidence ofvancomycin associated nephrotoxicityin critically ill patients: A preliminaryrandomizedcontrolledtrial.

Background Antioxidants show nephroprotective effect against vancomycin associated nephrotoxicity (VAN) in animals. This study aimed to assess the ascorbic acid nephro-protective role against VAN clinically. Methods Forty-one critically ill patients were randomly assigned to one of two groups: intervention group (vancomycin IV plus ascorbic acid, n=21) or control group (vancomycin IV only, n=20). Primary outcomes were the incidence of VAN and the absolute change in creatinine parameters, while mortality rate was the secondary outcome. Nephrotoxicity was defined as an increase in serum creatinine (S.cr) by at least 0.5 mg/dL or 50% of baseline for at least two successive measurements. This study is registered at Clinicaltrials.gov (NCT03921099), April 2019. Results Mean absolute S.cr increase was significant when compared between both groups, P-value = 0.036, where S.cr increased by 0.05(0.12) and 0.34(0.55) mg/dL in the intervention and control groups, respectively. Mean absolute Cr.cl decline was significant when compared between both groups, P-value = 0.04, where Cr.cl was decreased by 5.9(17.8) and 22.3(30.4) ml/min in the intervention and control groups, respectively. Incidence of VAN was 1/21(4.7%) versus 5/20(25%) in the intervention and control groups, respectively (RR: 0.19; CI: 0.024-1.49; P-value = 0.093). Mortality was higher in the control group; however, it was not statistically significant, P-value = 0.141. Conclusion Co-administration of ascorbic acid with vancomycin preserved renal function and reduced the absolute risk of VAN by 20.3%, however, the reduction in VAN incidence didn't reach statistical significance level. Further large multicenter prospective trials are recommended.

Antioxidant effect of ascorbic acid against cisplatin-induced nephrotoxicity and P-glycoprotein expression in rats

Cisplatin (CDDP) is a highly potent anticancer drug that is widely used in the treatment of several cancers. CDDP-induced nephrotoxicity (CIN) is one of the most significant adverse effects, and oxidative stress is thought to be one of the mechanisms underlying CIN. Although there are some studies available on the variability in transporter expression in the kidney after a single CDDP dose, none have reported the change in renal transporter expression after multiple CDDP dose administrations. P-glycoprotein (P-gp), a transporter, is reported to be induced by oxidative stress. Ascorbic acid is a vitamin with antioxidant potential and therefore, may regulate the expression of P-gp transporter and affect CIN. In the present study, our aim was to assess the variability in expression of several renal transporters after multiple CDDP dose administrations and the antioxidant effect of ascorbic acid against transporter expression and CIN. Multiple doses of CDDP affected markers of kidney injury and antioxidants in the kidneys. Also, the expression of P-gp, breast cancer resistance protein, and multidrug resistance-associated protein 4 was upregulated by CDDP. Using a normal kidney cell line, we demonstrated that ascorbic acid attenuated CDDP-induced cytotoxicity due to its high superoxide scavenging ability. CDDP and ascorbic acid were injected into rats once a week for three weeks, and it was observed that co-administration of ascorbic acid attenuated CIN and regulated antioxidant marker. In addition, ascorbic acid reduced P-gp expression, which was upregulated by CDDP. In conclusion, ascorbic acid may attenuate CIN and reverse P-gp-mediated changes in drug pharmacokinetics.

Evaluation of the Hepatoprotective And Nephroprotective Activities of Vitamin C and E in Paracetamol induced toxicity in Wistar Albino Rats

Free radical-mediated cell damage can be prevented by well-known antioxidant vitamins such as Vitamins E and C, and it has been reported that Paracetamol can cause hepatotoxicity at high doses. This study evaluated the efficacy of the combination of Vitamin C and Vitamin E in the prevention of renal and hepatic cell damage caused by paracetamol toxicity. Twenty-eight male albino rats were grouped into seven of four rats per group. Vitamin C at prophylactic dosage; (200mg, 150mg, 100mg, 50mg, 25mg) and Vitamin E at prophylactic dosage; (500iu, 400iu, 300iu, 200iu, 100iu) were administered orally to the rats in groups 1 through 5, respectively with concomitant administration 1000mg/kg bw of paracetamol twice daily for seven days. Group 6 was administered 1000mg/kg of paracetamol only (untreated), and Group 7 served as the normal control. The results revealed a significantly (P < 0.05) increase in serum ALT, AST, ALP, Urea and Creatinine of the group administered 1000mg/kg of paracetamol only. The prophylactic doses of ascorbic acid and α-tocopherol significantly (P < 0.05) decrease serum ALT, AST, ALP, Urea and Creatinine level compared to the untreated rats. This study validates that co-administration of ascorbic acid and α-tocopherol at the proposed prophylactic dosages could be used in the prevention of renal and hepatic cell damage caused by paracetamol toxicity.

The Radioprotective Effect of Ascorbic Acid and Kefir against Genotoxicity Induced by Exposure in Mice Blood Lymphocytes

The aim of this research was to determine how coadministration of ascorbic acid prior to the beginning of X-irradiation influences the lymphocyte DNA damage and also if the kefir supplementation to irradiated mice may alter the recovery procedure of lymphocyte genetic material injury. Following treatment of animals with these agents, the whole-body of mice were irradiated to 6 MV X-rays, then genotoxicity activity was investigated by comet assay. Our results show that the Total Comet Score (TCS) value was 1.39 and 1.5 fold less in the kefir and ascorbic acid groups respectively the following irradiation than in the irradiated mice only. Coadministration of ascorbic acid and kefir with 2 h, before relatively to 2 Gy radiation decreased DNA damage in lymphocyte blood cells. The antioxidant strength of ascorbic acid and kefir were investigated by the study of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging properties and also ferric reducing antioxidant power (FRAP) assay. Our results revealed that ascorbic acid and kefir show strong antioxidant activity by these methods. According to these results, it seems that ascorbic acid and kefir, as a free radical scavenging capacitiy, protect animal lymphocyte blood cells from radiation-induced DNA injury and genotoxicity.

Co-administration of ascorbic acid and α-tocopherol modifies ascorbic acid and attenuates p38, Akt, and TNF-α expression in spinal cord of rats with neuropathic pain

p38 and Akt plays an important role in neuropathic pain. p38 appears to regulate the SVCT-2 expression, a specific transporter for ascorbic acid (an important antioxidant and neuromodulator). Vitamins C and E induce antinociception and appear to affect p38, Akt, and SVCT-2, but it is unknown their effect on these molecules in spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. So, we investigated the effect of vitamins C + E on the expression of p38, Akt, and transporter SVCT-2 and ascorbic acid content in the lumbosacral spinal cord of rats with CCI. TNF-α mRNA level was also determined. Placement of four loose chromic thread ligatures around the sciatic nerve produced CCI. Ascorbic acid (vitamin C 30 mg/kg/day) + α-tocopherol (vitamin E 15 mg/kg/day) or vehicle (saline containing 1% Tween 80) were administrated (intraperitoneally) daily after CCI for 3 or 10 days. At the end of these periods, lumbosacral spinal cord was dissected out and used for assays. The vitamins prevented the increase in phosphorylated p38 and phosphorylated Akt and the decrease in SVCT-2 expressions, which were found in vehicle-treated CCI rats at days 3 and 10. Akt expression was reduced only at day 10. Vitamins also prevented the increase in ascorbic acid content and TNF-α level, which was found in vehicle-treated CCI rats. The changes in p-p38, p-Akt, ascorbic acid, SVCT-2, and TNF-α may be contributing to antinociception induced by vitamins C + E in rats with CCI.

Deleterious Effect of Maternal administration of Acrylamide on Lung Development and the Prospective Effect of Ascorbic Acid: Pertinent Role of Serum Endocan

Introduction: Acrylamide (ACR) is an environmental pollutant that is present in surrounding environment and Western-style carbohydrate-rich foodstuff and tobacco smoke.Aim of the Study: The aim of the study was to assess the potential histological changes in the lung of nascent rats as a consequence to maternal ACR administration and the possible protective role of ascorbic acid (ASA) in rat offspring.Materials and Methods: Pregnant rats were randomly assigned into four groups, negative control group, ASA group (100 mg/kg/day), ACR group (10 mg/kg/day) and ACR+ASA group. Ten pups from each group were sacrificed. Biochemical, histological and morphometric techniques were used to determine the effect of ACR and ASA on lung development in the offspring on postnatal days (PND) 2 and 21.Results: The results showed that ACR administration during gestational and lactation periods significantly increased the serum endocan and the lung malondialdehyde (MDA) but decreased the lung reduced glutathione (GSH) along with severe histopathological changes proved ultra-structurally. Morphometric results revealed significant increase thickness in interalveolar septa among ACR group. Concurrent administration of ASC with ACR during gestation period attenuated most of the cytoarchitecture alterations of the developing lungs.Conclusion: Maternal administration of acrylamide resulted in harmful impact on the lung histological structure of rat's offspring through its oxidative stress and inflammatory mechanisms. Co-administration of ASA along with ACR can ameliorate this deleterious impact through its antioxidant and anti- inflammatory properties

Complementary HPLC, in silico toxicity, and molecular docking studies for investigation of the potential influences of gastric acidity and nitrite content on paracetamol safety

This study was initiated for investigating the possible gastro-transformations that may affect the integrity and safety of the most commonly administered analgesic and antipyretic, paracetamol (PCM). Revisiting the safety of PCM has been accomplished by complementary HPLC, in silico toxicity prediction, and molecular docking approaches. The potential influences of the gastric-nitrite content on the chemistry of PCM were monitored via a simple and sensitive HPLC-UV method utilizing methanol: 0.05 M NaH2PO4.2H2O (40: 60, v/v) pH 2.5 as the mobile phase and a C18 column. This study revealed the likely transformation of PCM to three products which have been efficiently separated by the proposed HPLC method and identified by LC-ESI+/MS as 3-nitroparacetamol (P1), 5-nitro-3,3′-diparacetamol (P2), and 3,3′-diparacetamol (P3). The same products were also detected under the WHO-recommended standard test to evaluate the vulnerability of drugs to interaction with nitrite. The principle mechanism probably involves the in situ conversion of nitrite to the radical form NO2 that induces subsequent PCM radical formation, nitration, and dimerization. In silico toxicity prediction showed that P1 and P2 are mutagenic while P3 has a reproductive toxicity and P1 has acute rat toxicity 2 folds greater than PCM itself. P2 and P3 were also predicted to have androgenic toxicity by competing with testosterone for the androgen receptors and blocking the transmission of natural hormonal signal. The binding mode of the two compounds to the androgenic receptors has been explored via molecular docking study. These outcomes encourage the co-administration of ascorbic acid with PCM to inhibit these gastro-transformation reactions.

Effects of prenatal exposure to chrysotile asbestos on hippocampal neurogenesis and long-term behavioral changes in adult male rat offspring

Prenatal development is a critical period of life that many environmental pollutants have been suggested to influence fetal growth. Nevertheless, there are still a few investigations into the prenatal exposure to chrysotile asbestos and its neurodevelopmental and behavioral outcome in offspring.In this study, twenty-eight pregnant Wistar rats were divided into four groups and received three-times repeated intraperitoneal injections of normal saline, chrysotile, ascorbic acid and the combination of chrysotile and ascorbic acid on gestational days 11, 14 and 17. The maternal serum levels of malondialdehyde (MDA) and prooxidant-antioxidant balance (PAB) and hippocampal MDA content in adult male offspring were measured. At postnatal day (PND) 60, elevated plus maze was performed to determine anxiety-like behavior, also depression-like behavior was examined using a forced swim test at PND 61- 62. Thereafter, the quantitative analysis of Ki-67, NeuN and GFAP positive cells in the hippocampal dentate gyrus were studied by immunostaining.Our data showed that prenatal exposure to chrysotile increased the maternal serum level of MDA and PAB as well as hippocampal MDA content in adult male offspring, also increased the depression- and anxiety-like behaviors of adult male offspring and decreased the hippocampal Ki-67+, NeuN+ and GFAP+ cells in dantate gyrus of adult male offspring. However, co-administration of ascorbic acid and chrysotile decreased hippocampal lipid peroxidation and increased the Ki-67+, NeuN+ and GFAP+ cells in adult male offspring. In summary, these results indicated that oxidative stress induced by prenatal exposure to chrysotile, lead to the long-lasting decrease of the hippocampal cell proliferation and neuronal differentiation as well as astrogliosis of adult male offspring that exhibit more depression- and anxiety-like behaviors in adulthood and co-treatment of ascorbic acid with chrysotile asbestos attenuated the changes.

Effects of ascorbic acid treatment on developmental alterations in calcium-binding proteins and gamma-aminobutyric acid transporter 1 in the cerebellum of lead-exposed rats during pregnancy and lactation.

In the present study, we investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Female rats were randomly divided into the following groups: control, Pb, and Pb plus ascorbic acid (PA) groups. From one week prior to mating, female rats were administered Pb (0.3% Pb acetate in drinking water) and ascorbic acid (100 mg/kg, oral intubation). The chemical administration was stopped on postnatal day 21 when the morphology of the offspring's cerebellum is similar to that of the adult brain. The blood Pb level was significantly increased following long-term Pb exposure. Ascorbic acid reduced Pb levels in the dams and offspring. Nissl staining demonstrated that the number of Purkinje cells was significantly reduced following Pb exposure, while ascorbic acid ameliorated this effect in the cerebellum of the offspring. Calcium-binding proteins, such as calbindin, calretinin, and parvalbumin were commonly expressed in Purkinje cells, and Pb exposure and ascorbic acid treatment resulted in similar patterns of change, namely Pb-induced impairment and ascorbic acid-mediated amelioration. The gamma-aminobutyric acid transporter 1 (GABAT1) is expressed in the pinceau structure where the somata of Purkinje cells are entwined in inhibitory synapses. The number of GABAT1-immunoreactive synapses was reduced following Pb exposure, and ascorbic acid co-treatment prevented this effect in the cerebellar cortex. Therefore, it can be concluded that ascorbic acid supplementation to mothers during gestation and lactation may have potential preventive effects against Pb-induced impairments in the developing cerebellum via protection of inhibitory neurons and synapses.

Ascorbic Acid Supplementation Prevents the Detrimental Effects of Prenatal and Postnatal Lead Exposure on the Purkinje Cell and Related Proteins in the Cerebellum of Developing Rats.

We investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Prior to mating, rats were randomly divided into control, Pb, and Pb plus ascorbic acid (PA) groups. Pregnant rats were administered Pb in drinking water (0.3% Pb acetate), and ascorbic acid (100mg/kg) via oral intubation until the end of the experiment. Offspring were sacrificed at postnatal day 21, the age at which the morphology of the cerebellar cortex in developing pups is similar to that of the adult brain. In the cerebellum, Pb exposure significantly reduced Purkinje cells and ascorbic acid prevented their reduction. Along with the change of the Purkinje cells, long-term Pb exposure significantly reduced the expression of the synaptic marker (synaptophysin), γ-aminobutyric acid (GABA)-synthesizing enzyme (glutamic acid decarboxylase 67), and axonal myelin basic protein while ascorbic acid co-treatment attenuated Pb-mediated reduction of these proteins in the cerebellum of pups. However, glutamatergic N-methyl-D-aspartate receptor subtype 1 (NMDAR1), anchoring postsynaptic density protein 95 (PSD95), and antioxidant superoxide dismutases (SODs) were adversely changed; Pb exposure increased the expression of NMDAR1, PSD95, and SODs while ascorbic acid co-administration attenuated Pb-mediated induction. Although further studies are required about the neurotoxicity of the Pb exposure, the results presented here suggest that developmental Pb exposure disrupted normal development of Purkinje cells by increasing glutamatergic and oxidative stress in the cerebellum. Additionally, ascorbic acid co-treatment is beneficial in attenuating prenatal and postnatal Pb exposure-induced maldevelopment of Purkinje cells in the developing cerebellum.

Effect of ascorbic acid rich, micro-nutrient fortified supplement on the iron bioavailability of ferric pyrophosphate from a milk based beverage in Indian school children.

Nutritional anemia is a significant public health issue with 50-80% prevalence in Indian children. Fortification of food, specifically milk, with iron is a potential approach to increase dietary iron intake. Ferric pyrophosphate [Fe4(P2O7)3] is organoleptically neutral and is less soluble in acid medium and, further, has low bioavailability in milk. However, since ascorbic acid is a potent enhancer of iron absorption, the coadministration of ascorbic acid with Fe4(P2O7)3 might enhance the absorption of iron. We evaluated the effect of ascorbic acid on iron absorption from a Fe4(P2O7)3 and an ascorbic acid fortified milk beverage with respect to milk fortified with Fe4(P2O7)3 alone. A double-blind, two-way crossover, randomized study was conducted in 25 mildly anemic children. The test group received milk fortified with beverage powder containing 7 mg isotopically labeled iron (57Fe/58Fe) as Fe4(P2O7)3, equimolar proportions of ascorbic acid and 200 mg of calcium whereas control group received milk fortified with energy, calcium and iron equivalent beverage powder. Fractional iron absorption was measured by erythrocyte incorporation of stable isotopes of iron (57Fe/58Fe) in both the groups. The fractional iron absorption from the control drink was 0.80% (95% CI: 0.57, 1.12). Fortifying the milk with an equimolar amount of ascorbic acid increased the fractional iron absorption almost 2-fold to 1.58% (95% CI: 1.13, 2.22). The presence of ascorbic acid in an equimolar ratio with that of iron from Fe4(P2O7)3 salt in milk as a fortificant enhanced iron absorption when compared to milk fortified with only Fe4(P2O7)3.

Histological and Biochemical Studies of the Actions of a Multi-herbal Tea on the Testis in Wistar Rats

Tea is consumed almost worldwide as a beverage and for its perceived health benefits. Tea has been used in folk medicine to treat a wide range of disorders. Tea is believed to be safe but recent studies suggest that under certain conditions, components of tea may be toxic to the liver and testis in rats. This study examined the effects of a multi-herbal tea on sperm parameters, markers of oxidative stress and histology in the testes of Wistar rats. We analysed histology of testis, and estimated sperm parameters and markers of oxidative stress such as catalase and reduced glutathione in 3 groups of rats that had been treated with 150 mg/kg of a tea extract for 4 and 8 week durations. One of the treated groups received ascorbic acid along with the extract. Our results show that the extract caused a significant reduction in all sperm parameters, with a 25% Original Research Article Akaahan et al.; JAMPS, 8(1): 1-9, 2016; Article no.JAMPS.25296 2 and 50% reduction in sperm count and motility respectively. Tea also caused oxidative stress with raised levels of malondialdehyde and reduced levels of catalase and glutathione. The extract also induced considerable degenerative changes in histology of the testes. Co-administration of ascorbic acid resulted in significant improvement in all sperm parameters and protection of testes from histological damage. We conclude that tea may be generally safe to take but at certain dosage and length of use, multi-herbal teas can impair spermatogenesis and damage the histology of testicular tissue, at least in rats.

Ascorbic acid co-administration with artemisinin based combination therapies in falciparum malaria.

Malaria infection poses a serious public health problem in endemic countries. As per World Malaria Report 2015, it is estimated that 3.2 billion people in 97 countries are at risk of being infected with malaria; 214 million cases of malaria with 4,38,000 malaria induced deaths are reported during the year1. Clinical consequences of malaria result primarily from parasitic invasion of red blood cells (RBCs). Inside the RBCs, the parasite metabolizes the host haemoglobin in the acidic environment of the parasite's food vacuole. This leads to production of free haem which contains Fe2+ atoms that can catalyze Fenton and Haber-Weiss reactions, generating the radicals which can cause extensive molecular damage2. Haemolysis of infected red cells releases free haem which may be responsible for an external oxidative stress on both infected and non-infected RBCs2 and may be one of the factors contributing to destruction of normal red cells. Presence of pro-oxidants in plasma of patients suffering from acute falciparum malaria has been demonstrated by measurement of the erythrocyte thiobarbituric acid-reactive substance concentrations3. The parasite develops antioxidant mechanisms partly through reducing its own generation of reactive oxygen species and partly through increased synthesis of reduced glutathione and thioredoxin reductase system2. During intraerythrocytic development of Plasmodium falciparum, a large number of parasite proteins move beyond its own plasma membrane and associate with RBC membrane cytoskeletal proteins. Parasite and host red cell cytoskeletal protein interactions lead to formation of large molecular complexes which appear as electron dense “knobs” on the RBC surface. These changes lead to alterations in the rheological properties of infected red cells which become less deformable and more adhesive4.

Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study.

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects.