Administration Of Ascorbic Acid Research Articles

Characteristics of proliferation and apoptosis of hepatocytes after administration of ascorbic acid in a model of radiation hepatitis

BACKGROUND: Radiation hepatitis with the development of radiation-induced acute liver failure is considered one of the most serious complications of radiotherapy for malignant neoplasms of the liver, abdominal organs, or whole body irradiation. However, the exact mechanisms of radiation-induced liver cell death have not been fully elucidated, and therefore the study of changes in the proliferative-apoptotic ratio in liver structures remains relevant, and pre-irradiation administration of ascorbic acid can potentially protect them from the effects of electron irradiation.
 AIM: assessment of proliferation and apoptosis of hepatocytes after administration of ascorbic acid in a model of radiation hepatitis.
 METHODS: Wistar rats (Rattus Wistar; n=40) were divided into four experimental groups: I – control (n=10); II (n=10) – fractional irradiation with electrons in a total irradiation dose of 30 Gy; III (n=10) – administration of ascorbic acid before electron irradiation; IV (n=10) – administration of ascorbic acid. Animals of all groups (I – IV) were removed from the experiment a week after the last fraction. Morphological and immunohistochemical (with antibodies to Ki-67 and caspase-3) studies were carried out.
 RESULTS: A week after electron irradiation, a sharp decrease in the proportion of Ki-67-positive hepatocytes in combination with an increase in immunolabeling with antibodies to caspase-3 was observed in group II. During the administration of ascorbic acid in group III, less pronounced depth and range of liver damage was noted, confirmed by morphological and immunohistochemical methods (less pronounced decrease in the level of Ki-67 expression and an increase in the proportion of caspase-positive hepatocytes compared to the control) methods.
 CONCLUSION: An immunohistochemical study of proliferation and apoptosis of hepatocytes revealed that a week after fractional electron irradiation in SOD 30 Gy, there is a decrease in mitotic activity and an increase in cell death, and pre-irradiation administration of ascorbic acid helped level out the detected changes, which indicates its protective effect.

Ascorbic acid predominantly kills cancer stem cell-like cells in the hepatocellular carcinoma cell line Li-7 and is more effective at low cell density and in small spheroids

The development of therapies that target cancer stem cells (CSCs) is an important challenge in cancer research. The antioxidant system is enhanced in CSCs, which may lead to resistance to existing therapies. Ascorbic acid (AA) has the potential to act as both an antioxidant and a pro-oxidant agent, but its effects on CSCs are a subject of current research. Here, we investigated the effect of AA focusing specifically on CSCs with the hepatocellular carcinoma cell line Li-7. The Li-7 cell line is heterogenous consisting of CD166- and CD166+ cells; CD166- cells include CSC-like cells (CD13+CD166- cells) and CD13−CD166- cells that can revert to CD13+CD166- cells. The addition of AA to the culture medium caused cell death in both cell populations in CD166- cells in a concentration dependent manner. In contrast, AA administration had a limited effect on CD166+ non-CSC cells. The level of reactive oxygen species after AA treatment was elevated only in CD166- cells. The effect of AA only occurred at low cell densities in 2D and 3D cultures. In a mouse tumor model injected with Li-7 cells, intraperitoneal administration of AA failed to prevent tumor formation but appeared to delay tumor growth. Our findings shed light on why AA administration has not become a mainstream treatment for cancer treatment; however, they also show the possibility that AA can be used in therapies to suppress CSCs.

Effect of ascorbic acid supplementation on skin wound healing

Ascorbic acid is essential for proper synthesis of collagen fiber and intercellular.ground substance of connective tissueObjective of this study was to determine the effect of ascorbic acid supplementationmg once daily for l0 days in the treatment of wound skin incision about 2cm in555.length and 4mm in depthThirteen albino rabbit were used in this study (eight rabbits represent experimental.)group while five represent as a control groupThe result of general histological observation revealed rapid and active healingprocess through complete epithelization of the surface of incision site and colla enousg . .fibrous tissue formation in the incision wound of animals with ascorbic acidadministration while in control group incomplete epithelization and incomplete healing of.connective tissue of skin woundIt was concluded that the administration of ascorbic acid might be sufficient to promote wound healing

Successful Treatment, with Chemotherapy and Intravenous Administration of Ascorbic Acid, of a Patient with Peripheral T-Cell Lymphoma, Not Otherwise Specified

Here, we report the case of a 64-year-old man with peripheral T-cell lymphoma, not otherwise specified, who complained of diffuse lymphadenopathy and pancytopenia. This patient received the CHOP regimen followed by the CHP plus brentuximab vedotin regimen, and eventually experienced severe adverse effects, such as leukocytopenia and thrombocytopenia. He was then intravenously administered high doses of ascorbic acid to enhance the effects of chemotherapy drugs and reduce the intensity of the side effects. Positron emission tomography-computed tomography revealed a complete response of the lesions to combination therapy. This case report demonstrated the feasibility, efficacy, and acceptable toxicity of high-dose ascorbic acid in patients undergoing chemotherapy.

Ascorbic acid prevents stress-induced hypercoagulability in overweight and obese individuals

Ascorbic acid (AA) may contribute to restoring hemostatic balance after mental stress (MS) in overweight/obese adults. We aimed to determine the effects of AA administration on hemostatic responses to MS in overweight/obese men. Fourteen overweight/obesity men (27 ± 7 years; BMI: 29.7 ± 2.6 kg m−2) performed the Stroop color-word stress task for 5 min after non-simultaneous infusion of placebo (PL, 0.9% NaCl) and AA (3 g). Blood was collected at baseline, during MS, and 60 min after MS to measure: activated partial thromboplastin time, prothrombin time, and fibrinogen concentration, by coagulometer; platelet-derived microvesicles (PMV, mv/μL), by flow cytometry; nitrite (μM), by chemiluminescence. In PL session, MS led to decreases in PTs (stress, p = 0.03; 60 min, p < 0.001), PT-INR (stress, p < 0.001; 60 min, p < 0.01), aPTTs (60 min, p = 0.03), aPTT ratio (60 min, p = 0.04) and fibrinogen (60 min, p = 0.04), while increased PT activity (60 min, p = 0.01) when compared to baseline. Furthermore, AA increased PTs (60 min, p < 0.001), PT-INR (60 min, p = 0.03) and decreased PT activity (60 min, p < 0.001) and fibrinogen (stress, p = 0.04) when compared to PL. Nitrite was increased in response to stress during AA session (p < 0.001 vs PL). There was no difference in PMV. Ascorbic acid prevented the impaired hemostatic profile and improved nitrite response to stress in the overweight and obese adults.

Ascorbic acid induces ferroptosis via STAT3/GPX4 signaling in oropharyngeal cancer

Ferroptosis is recognized as a new type of regulated cell death initiated by iron-dependent accumulation of lipid peroxidation. Recent studies have shown that the administration of ascorbic acid (AA) preferentially kills tumor cells by impairing iron metabolism and exerting pro-oxidant effects. Despite mounting evidence indicating the anticancer potential of AA, the underlying molecular mechanisms remain unknown. In this study, we demonstrated that AA decreased cell viability and Ki67 expression, along with its accumulation in the G0/G1 phase in FaDu and SCC-154 cell lines. Furthermore, AA exposure induced morphological changes in mitochondria associated with ferroptosis. AA-induced ferroptosis is accompanied by depletion of glutathione (GSH) and increased levels of ferrous ions (Fe2+), reactive oxygen species (ROS), and malondialdehyde (MDA). However, these ferroptotic effects were ameliorated by deferoxamine and N-acetylcysteine. Network pharmacology results showed that signal transducer and activator of transcription 3 (STAT3) is a key target of AA against oropharyngeal cancer. AA markedly downregulates the relative mRNA expression of STAT3 and glutathione peroxidase 4 (GPX4). Immunoblotting indicated that the protein levels of p-STAT3, STAT3, and GPX4 in FaDu and SCC-154 cells decreased significantly in response to AA treatment. Mechanistically, a chromatin immunoprecipitation assay confirmed that AA exposure reduced STAT3 expression in the GPX4 promoter region. Additionally, AA-induced inhibition of cell growth and ferroptosis was suppressed by STAT3 and GPX4 overexpression, respectively. In summary, AA inhibited oropharyngeal cancer cell growth in vitro by regulating STAT3/GPX4-mediated ferroptosis, which may provide a novel theoretical basis for the clinical treatment of oropharyngeal cancer with AA.

Administration of combined exogenous L-arginine and ascorbic acid attenuates potassium bromate-induced renal and hepatic toxicity

Background: The use of potassium bromate (KBrO3) as food additive is still widespread and there is need to search for agents with protective effect against KBrO3-induced toxicity.&#x0D; Objective: In this study, the protective effects of L-arginine, ascorbic acid, and their combined regimen on KBrO3-induced renal and hepatic toxicity were investigated in Wistar rats.&#x0D; Methods: Five groups of male rats were used for the study. Group A was given distilled water (control), and group B was treated with KBrO3 only. In addition to KBrO3, groups C, D, and E were given L-arginine, ascorbic acid, and combined L-arginine and ascorbic acid respectively. After 28-day treatment, blood samples were taken for biochemical analysis; liver and kidney were harvested for histological examination.&#x0D; Results: KBrO3 significantly (p &lt; 0.05) raised serum levels of creatinine, urea, ALT, and AST compared to distilled water-treated control. Levels of SOD, CAT, and GPx were also significantly reduced. No significant changes in these parameters were observed with ascorbic acid and L-arginine given separately. Treatment with combined regimen of L-arginine and ascorbic acid resulted in significant (p &lt; 0.05) reduction in the serum levels of creatinine, AST and ALT, and significant increase in the serum levels of SOD, CAT and GPx compared to the control. The distortions induced by KBrO3 in the structural architecture of renal and hepatic tissues were largely reduced in rats treated with combined ascorbic acid and L-arginine.&#x0D; Conclusion: The study showed that L-arginine and ascorbic acid synergistically attenuate KBrO3-induced renal and hepatic toxicity.

Effects of Pyrethroid Exposure on Testicular Histopathology and Biochemistry in Adult Male Wistar Rats: Evaluation of Ascorbic Acid and Alpha-Tocopherol Administration

Effects of Pyrethroid Exposure on Testicular Histopathology and Biochemistry in Adult Male Wistar Rats: Evaluation of Ascorbic Acid and Alpha-Tocopherol Administration

STATE OF THE XENOBIOTICS BIOTRANSFORMATION SYSTEM IN THE LIVER MICROSOMAL FRACTION OF RATS UNDER THE EFFECTS OF SODIUM BENZOATE AND ASCORBIC ACID

The combined effect of food preservatives – sodium benzoate and ascorbic acid on the state of monooxygenase system (MOS) components in the microsomal fraction of rat liver cells are studied in the paper. Changes in the level of cytochrome P450 and cytochrome b5, as well as the rate of reduction-oxidation of these hemoproteins in the microsomal fraction of the rat liver under conditions of administration of sodium benzoate and ascorbic acid were studied. During the experiment, rats were divided into four groups: group I – control (intact animals); group II – rats that were injected with ascorbic acid at a dose of 30 mg per kg of animal weight; group III – rats that were injected with sodium benzoate at a dose of 750 mg per kg of animal weight; group IV – rats that were injected with sodium benzoate 30 minutes before the introduction of ascorbic acid. Sodium benzoate and ascorbic acid were administered per os daily for 21 days. Animals were euthanized under light ether anesthesia on the 21st day after the start of administration of sodium benzoate and ascorbic acid. It was established that the three-week introduction of sodium benzoate into the body of animals leads to a decrease in the level of cytochrome P450, which occurs due to an increase in the rate of transition of cytochrome P450 into its inactive form P420. It was shown that along with the decrease in cytochrome P450 in the microsomal fraction of the liver, the level of cytochrome b5 decreases with a simultaneous increase in the rate of reduction and oxidation of this hemoprotein. Sodium benzoate exhibits a higher destructive effect when it is combined with ascorbic acid, which is expressed by a decrease in the level of MOS hemoproteins and may be a consequence of dangerous metabolites formation in the body - benzoic acid and benzene.

The Protective Role of Prenatal Administration of Ascorbic Acid on Autistic-like Behavior in a Rat Model of Autism

BackgroundAutism is a complicated neurodevelopmental disorder characterized by several behavioral impairments. The pathology of autism is complex and not fully known. Several recent studies have shown alterations in the activities of antioxidant enzymes in autism. Vitamin C is a potent antioxidant that is present in high concentrations in the brain and acts as a neuromodulator. Prefrontal abnormality has been hypothesized to underlie autistic symptoms. The present study investigated the protective effect of prenatally Vitamin C on autistic-like behaviors, oxidative stress status, and histopathological change of prefrontal in valproic acid (VPA) rat model of autism. MethodThe model of autism was induced by subcutaneous administration of Valproic acid (600mg/kg) to pregnant rats at gestational day 12.5. Vitamin C was administered 600mg/L in drinking water from the 5th day of gestaion (GD5) up to postnatal day 23 (PND23). Thirty-two rat offspring were divided into four groups: Control, Vitamin C, VPA, and Vitamin C + VPA. The offspring were tested for repetitive behaviors and cognitive ability with a Y-maze task and social interaction with a play behavior task on 31st of Postnatal days. Glutathione (GSH), superoxide dismutase (SOD) activity, and the histological change in the prefrontal lobe were assessed at the end of the study. The number of neurons from the left prefrontal lobe was counted in duplicate from slides stained with hematoxylin-eosin. ResultsIn the Y-maze apparatus, spontaneous alteration significantly decreased in the prenatal VPA treated rats compared to control rats showing autistic-like behavior; pre and postnatal Vitamin C treatment increased the alternation indicated benefit effect of Vitamin C. Prenatal VPA treatment impaired play behavior such as sniffing, grooming and darting. Vitamin C treatment attenuated the problems in male offspring social behavior. Histological examination showed an increase in the number of cells in the prefrontal cortex of valproic acid offspring rats compared to other groups. Moreover, prenatal VPA decreased antioxidant enzyme activities in the cortex (PFC) attenuated by Vitamin C administration. ConclusionThe present study showed that valproic acid induced oxidative stress and neural changes in the prefrontal lobe when administered prenatally which in turn may cause the development of some autistic-like behaviors, and vitamin C may reduce this symptom with its antioxidant effects

Effects of intravenous administration of ascorbic acid (vitamin C) on oxidative status in healthy adult horses.

Ascorbic acid (AA) is an antioxidant that might be beneficial for adjunctive treatment of sepsis in horses. The optimal dose and effects on oxidative status are unknown. Ascorbic acid administration will increase plasma AA concentrations and decrease determinants of reactive oxygen metabolites (dROM), basal and stimulant-induced intraerythrocytic reactive oxygen species (ROS) concentrations, and stimulant-induced neutrophil ROS production, and increase plasma antioxidant capacity (PAC) in a dose-dependent manner. Eight healthy horses. Randomized placebo-controlled crossover study. Each horse received 4 single-dose IV treatments including AA at 25, 50, and 100 mg/kg and saline (placebo) with each treatment separated by ≥1 week. Blood was collected at baseline, 2 and 6 hours for assessment of plasma dROM and PAC via photometer, intraerythrocytic ROS by flow cytometry, and stimulant-induced neutrophil ROS by a fluorometric assay. Plasma AA concentrations were measured by high-performance liquid chromatography/electrochemical detection. Ascorbic acid at 100 mg/kg resulted in decreased dROM 2 hours after treatment (P = .03, 95% CI 5.51-121.2, point estimate 63.3). There was no effect of AA on basal or stimulant-induced intraerythrocytic ROS (P = .88, 95% CI -0.156 to 0.081, point estimate -0.037; P = .93, 95% CI -0.123 to 0.112, point estimate -0.006, respectively), basal or stimulant-induced neutrophil ROS (P ≥ .12, 95% CI -644.9 to 56.2, point estimate -294.4), or PAC (P ≥ .64, 95% CI -1567 to 463.4, point estimate -552.0) at any dose or timepoint. Plasma AA concentrations increased in a dose-dependent manner. High-dose administration of AA might provide antioxidant benefits in horses.

The protective role of vitamins C and E in steroid-induced femoral head osteonecrosis: An experimental study in rats.

This study aimed to determine whether vitamin C (VC) and vitamin E (VE) can effectively protect the femoral head and reduce the risk of developing osteonecrosis in rats that have been treated with steroids. The study was conducted on 30 young adult male Sprague-Dawley rats (mean weight: 356±18 g; range, 330 to 375 g), which were randomly assigned to one of five groups. The control group received saline solution, while the other groups were given lipopolysaccharide/methylprednisolone (LPS/MPS) to induce osteonecrosis. Three groups in which osteonecrosis was induced were also intraperitoneally administered either VC, VE, or both once a day for four weeks. Intracardiac blood samples were taken at the end of the fourth week for biochemical examination, and the rats were then sacrificed under general anesthesia. After sacrification, right femurs were removed for histopathological, immunohistochemical, and radiologic examinations. The results showed that the mean trabecular number increased significantly in the VC+VE group. There was a substantial decrease observed in the mean trabecular separation within the LPS/MPS group compared to the control group, although trabecular separation decreased in all three vitamin groups compared to the LPS/MPS group. The surface area/bone volume was significantly increased in the VC+VE group compared to the LPS/MPS group. Histological, immunohistochemical, and radiological examinations showed that the administration of VC and VE significantly reduced oxidative stress, inflammation, and microvascular dysfunction in rats with steroid-induced femoral head osteonecrosis. This study suggests that VC, VE, and particularly VC+VE have a protective effect on the femoral head in rats with steroid-induced femoral head osteonecrosis. These findings may lead to new treatment options for patients.

Effect of adjuvant thiamine and ascorbic acid administration on the neurologic outcomes of out-of-hospital cardiac arrest patients: A before-and-after study

AimThis study aimed to evaluate the impact of early thiamine and ascorbic acid administration on the neurologic outcome in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). MethodsThis before-and-after cohort study used data extracted from two hospitals of the Korean Hypothermia Network prospective registry. The treatment group incorporated patients enrolled from December 2019 to May 2021, that received intravenous thiamine (200 mg) and ascorbic acid (3 g) at 12-hour intervals for a total of six doses. The control group incorporated those enrolled from May 2018 to November 2019. The one-month good neurologic outcome, defined as a Cerebral Performance Category score ≤ 2, between the groups was evaluated using inverse probability of treatment weighting (IPTW). ResultsAmong the 234 OHCA survivors with TTM, 102 were included in the treatment group and 132 were included in the control group. The one-month (31.4 % vs. 29.5 %, respectively; P = 0.76) good neurologic outcome rates did not differ between the treatment and control groups. After adjusting using the IPTW, vitamin supplementation was not associated with good neurologic outcome (odds ratio [OR], 1.134; 95 % confidence interval [CI], 0.644–1.999; P = 0.66). In subgroup analysis, vitamin administration was significantly associated with a good neurologic outcome in older (≥65 years) patients (adjusted OR, 5.53; 95 % CI, 1.21–25.23; P = 0.03). ConclusionAdjuvant thiamine and ascorbic acid administration in OHCA survivors with TTM did not improve their neurologic outcome after one month. Further clinical trials are warranted.

High-dose ascorbic acid potentiates immune modulation through STAT1 phosphorylation inhibition and negative regulation of PD-L1 in experimental sepsis.

Sepsis is a complex, multifactorial syndrome characterized by a dysregulated host response to infection, leading to severe organ dysfunction and high mortality rates among critically ill patients. Hypovitaminosis C and vitamin C deficiency are frequently observed in septic patients, prompting interest in the potential therapeutic role of ascorbic acid. Although intravenous administration of ascorbic acid has been investigated in multiple clinical trials for sepsis treatment, the specific immunomodulatory mechanisms underlying its effects remain elusive. This study aimed to investigate the protective effects of high-dose ascorbic acid on experimental sepsis. Results show that intravenous administration of high-dose ascorbic acid (250mg/kg) attenuated sepsis-induced organ dysfunctions in a cecal ligation and puncture (CLP)-induced septic mouse model. Ascorbic acid improved splenic cell apoptosis and increased the number of CD3+ T cells in septic mice induced by CLP. Furthermore, ascorbic acid downregulated PD-L1 expression in livers, reduced PD-1 expression in spleens, and inhibited the phosphorylation of STAT1 at Y701 in multiple organs of CLP-induced septic mice. The in vitro experiments also revealed that 800μM ascorbic acid suppressed STAT1 phosphorylation and inhibited lipopolysaccharide (LPS) and IFN-γ-induced PD-L1 expression in macrophages. These findings suggest that ascorbic acid prevents sepsis-associated organ dysfunction through the p-STAT1/PD-L1 signaling pathway. Our study provides new insights into the potential therapeutic use of ascorbic acid in sepsis.

Ascorbic Acid for Methemoglobinemia Treatment: A Case Report and Literature Review.

Ascorbic acid has been proposed as an alternative treatment for methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, its efficacy has never been compared to that of methylene blue given the inability of patients with G6PD deficiency to receive methylene blue. We present a case of methemoglobinemia treated with ascorbic acid in a patient without G6PD deficiency who had previously received methylene blue. A 66-year-old male was treated for methemoglobinemia deemed to be secondary to benzocaine throat spray. He received intravenous (IV) methylene blue but had a severe reaction: diaphoresis, lightheadedness, and hypotension. The infusion was stopped prior to completion. Approximately 6 days later he presented with methemoglobinemia following an additional overconsumption of benzocaine and was treated with ascorbic acid. In both instances his methemoglobin levels were >30% on arterial blood gas on admission and decreased to 6.5% and 7.8%, respectively, after administration of methylene blue and ascorbic acid. Ascorbic acid had a similar effect on decreasing the concentration of methemoglobin compared to methylene blue. Further research into use of ascorbic acid as a recommended agent for treatment of methemoglobinemia is warranted.

Effect of ascorbic acid on collagen and some inflammatory mediators in rats

Musculoskeletal injuries as a kind of trauma that the human body is exposed to, adversely affect the quality of life and workforce of individuals due to restriction of movement function. This study aimed to evaluate the effects of dose-dependent ascorbic acid (AA) administration on the repair process after gastrocnemius muscle injury in rats. In this study, 5-month-old 66 male Wistar Albino rats were used and rats were randomly divided into 6 groups of 11 each [control, muscle injury, healthy (with 5 mg/10 mg/kg/day AA-treated group), injury (with 5 mg/10 mg/kg/day AA-treated group)]. A linear incision was made in the gastrocnemius muscle of thirty-three animals included in the muscle injury groups. AA (5-10 mg/kg/day) was administered to the four groups intraperitoneally just after surgery once a day. Animals were sacrificed twenty-one days later. Blood and tissue samples were used for cytokine, collagen, and histological measurements. It was found that a dose of 5 mg/kg/day AA administration reduced serum IL-6 and muscle tissue TNF-α levels, and increased liver tissue IL-10 levels. Muscle tissue collagen levels were not statistically different between the groups in parallel with our histological results. In our study, it was demonstrated that vitamin C has effects on inflammatory mediators during muscle tissue repair to explain the mechanism detailed molecular analyzes are needed.

Human Colon Cancer HT29 Cell Line Treatment with High-Dose LAscorbic Acid Results to Reduced Angiogenic Proteins Expression and Elevated Pro-apoptotic Proteins Expression.

Some studies have shown anticarcinogenic effects of high dose L-Ascorbic Acid. However, there are controversies around the therapeutic administration of Ascorbic acid as an anticancer medicine. We conducted a case-control study to investigate the role of pharmacologic concentration of Ascorbic acid on viability and angiogenesis of the human colon cancer (HT29) cell line. The HT29 cells were cultured in DMEM-HG and treated with 10 mM ascorbic acid for 3h. The culture medium was exchanged, and after incubation at 37 ºC for 24 h, the cells were collected and utilized to evaluate viability, ROS production, gene expression and protein expression levels. The control group consisted of untreated HT29 cells. The viability of the cells was determined using the MTT method. Moreover, Nitro Blue Tetrazolium (NBT) was used to detect the ROS production capacity. The mRNA transcript's level and protein expression were evaluated by Real-time PCR and Western blotting, respectively. The ascorbic acid-treated group showed a significant increase in ROS production and an obvious reduction in viability compared to the control group. The treated group showed significantly increased levels of both early apoptotic markers (Bax, Cyt C, Caspase3, and Caspase 9) and late apoptotic markers (Caspase 8). Bcl2 expression showed significantly decreased levels relative to the control group. Ascorbic acid therapy substantially reduced the expression of bFGF, bFGFR, PDGF, PDGFR and PLC- γ compared to the control group. The results confirm that high-dose L-ascorbic acid reduces HT29 cell line viability in vitro.

High-dose intravenous versus low-dose oral vitamin C in burn care: potential protective effects in the severely burned: a retrospective cohort study.

The hospital burn database was used to obtain data on all patients with second-degree or deeper burns of 20% total-body-surface-area or greater. Fourteen patients were selected at random to receive a scheduled dose of 1250mg intravenous ascorbic acid every 6h for 72h. This was considered the high-dose group. During same period, 40 patients received scheduled 500mg oral ascorbic acid every 6h for 72h and this was considered the low-dose group. We gathered sociodemographic and clinical variables associated with ascorbic acid dosing. In our study, statistically significant variables were fluid requirements (p<0.001), hospital stay (p=0.011), length of time intubated on ventilator (p<0.001), colloids used (p=0.002), and total procedures required (p=0.014). Despite higher modified Baux predicted mortality in the high-dose group (10 patients vs. 24 patients, p=0.026) there was no noted significant association in days until the first infection and mortality rate (p=0.451 and 0.326, respectively). The calculated modified Baux predicted a higher mortality rate with the higher dosing group, yet this study did not find a mortality difference between the groups. We speculate that high-dose intravenous ascorbic acid may have protective effects in burn resuscitation. This finding may support some previous studies that found that high-dose ascorbic acid may improve clinical outcomes.

The neuroprotective effect of ascorbic acid against imidacloprid-induced neurotoxicity and the role of HO-1 in mice.

Imidacloprid (IMI) is not only a neurotoxic agricultural pesticide but also a possible food contaminant. The aims of this study were to (1) explore the relationship between recurrent IMI administration and neuronal toxicity in mice and (2) evaluate the potential neuroprotective effect of ascorbic acid (AA), a substance with significant free radical scavenger and having property to block the inflammatory pathways. Mice were categorized as naïve controls (administered vehicles for 28 days); the IMI-treatment animal group (administered po 45-mg/kg body weight of IMI per day for 28 days); and the IMI + AA treatment animal group (administered the same IMI dose + 200 mg/kg of AA orally for 28 days). On day 28, memory losses were assessed using the Y-maze and novel target identification behavioral tests. Mice were sacrificed 24 h after the final IMI treatments, as well as hippocampus tissues, were utilized to determine histological assessments, oxidative stress biomarkers, and Heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression levels. The findings demonstrated that IMI-treated mice had substantial impairment of spatial and non-spatial memory functions, as well as reduced antioxidant enzyme and acetylcholinesterase activity. The AA neuroprotective action was achieved through the suppression of the HO-1 expression as well as the stimulation of Nrf2 expression in hippocampal tissues. In summary, recurrent IMI exposure causes oxidative stress and neurotoxicity in mice, and the administration of AA significantly reduces the IMI toxicity possibly by the activation of the HO-1/Nrf2 pathway.

Ascorbic acid reduces insulin resistance and pancreatic steatosis by regulating adipocyte hypertrophy in obese ovariectomized mice.

Ascorbic acid has been suggested to regulate obesity in obese male rodents.Moreover, increased adipocyte size has been associated with metabolic disease. Thus, we investigated the effects of ascorbic acid on adipocyte hypertrophy and insulin resistance in high-fat diet (HFD)-induced obese ovariectomized (OVX) C57BL/6J mice, an animal model of obese postmenopausal women. Administration of ascorbic acid (5%w/w in diet for 18 weeks) reduced the size of visceral adipocytes without changes in body weight and adipose tissue mass in HFD-fed obese OVX mice compared with obese OVX mice that did not receive ascorbic acid. Ascorbic acid inhibited adipose tissue inflammation, as shown by the decreased number of crown-like structures and CD68-positive macrophages in visceral adipose tissues. Ascorbic acid-treated mice exhibited improved hyperglycemia, hyperinsulinemia, and glucose and insulin tolerance compared with nontreated obese mice. Pancreatic islet size and insulin-positive β-cell area in ascorbic acid-treated obese OVX mice decreased to the levels observed in low-fat diet-fed lean mice. Ascorbic acid also suppressed pancreatic triglyceride accumulation in obese mice. These results suggest that ascorbic acid may reduce insulin resistance and pancreatic steatosis partly by suppressing visceral adipocyte hypertrophy and adipose tissue inflammation in obese OVX mice.