Daily pattern of pituitary glutamine, glutamate, and aspartate content disrupted by cadmium exposure

Cadmium is a neurotoxic heavy metal and is considered endocrine disruptor. In this work, we investigate the effects of cadmium on the 24 h changes of aspartate, glutamate, and glutamine content in the pituitary. Adult male Sprague–Dawley rats were treated with 25 or 50 mg/l of cadmium chloride (CdCl₂) in the drinking water for 30 days. Metal exposure with the lowest dose induced the disappearance of the nocturnal peak of anterior pituitary amino acid content, and the appearance of a peak of glutamine concentration during the resting phase of the photoperiod. After exposure to 50 mg/l of CdCl₂, the peaks of anterior pituitary amino acid content at 12:00 and 00:00 h disappeared, and two minimal values at these same hours and a peak at 08:00 h appeared. In the posterior pituitary, cadmium treatment with the lowest dose induced the appearance of a peak of aspartate and glutamate concentration at 12:00 h, and the disappearance of the peak of glutamine content at 16:00 h. After exposure to 50 mg/l of CdCl₂ aspartate and glutamate daily pattern presented two maximal values between 00:00 and 04:00 h, and the metal abolished glutamine daily pattern. These results suggest that cadmium disrupted aspartate, glutamate, and glutamine daily pattern in the pituitary.     

Possible role of glutamate, aspartate, glutamine, GABA or taurine on cadmium toxicity on the hypothalamic pituitary axis activity in adult male rats

This work was designed to evaluate the possible changes in glutamate, aspartate, glutamine, GABA and taurine within various hypothalamic areas the striatum and prefrontal cortex after oral cadmium exposure in adult male rats, and if these changes are related to pituitary hormone secretion. The contents of glutamine, glutamate, aspartate, GABA and taurine in the median eminence, anterior, mediobasal and posterior hypothalamus, and in prefrontal cortex in adult male rats exposed to 272.7 mol l^–1 of cadmium chloride (CdCl₂) in the drinking water for one month. Cadmium diminished the content of glutamine, glutamate and aspartate in anterior hypothalamus as compared to the values found in the untreated group. Besides, there is a decrease in the content of glutamate, aspartate and taurine in the prefrontal cortex. The amino acids studied did not change in median eminence, mediobasal and posterior hypothalamus or the striatum by cadmium treatment. Plasma prolactin and LH levels decreased in rats exposed to the metal. These results suggest that (1) cadmium differentially affects amino acid content within the brain region studied and (2) the inhibitory effect of cadmium on prolactin and LH secretion may be partially explained by a decrease in the content of both glutamate and aspartate in anterior hypothalamus, but not through changes in GABA and taurine.     

Differential changes of neuroactive amino acids in samples obtained from discrete rat brain regions after systemic administration of saxitoxin

Aspartic acid, glutamic acid, γ-amino-n-butyric acid (GABA) and 2-aminoethanesulfonic acid are neuroactive amino acids. They are found in the central rat nervous system. Here, we have studied if a relationship exists between the presence of saxitoxin (STX) a paralytic poisoning shellfish (PSP) and the neuroactive amino acids. Samples of striatum (S), hypothalamus (H), mid brain (MB), frontal cortex (FC), brain stem (BS), right hemisphere (RH) and left hemisphere (LH) of rat brain were collected and analyzed for neuroactive amino acids (AAn_t) by Aswad method (1984). Experiments, consisting of intraperitoneal injection of SXT (5 and 10 μg kg^?1 body weight) to young male rats, evoked significant changes in AAn_t above basal values. Aspartic and glutamic acid significantly increased for RH and LH (after 30 min the increased was 116% and 210%, P ≤ 0.001 over basal values, respectively). On the other hand, aspartic, glutamic, taurine and GABA significantly decreased for S (after 30 min the decreased was 77.4%; 84%; 93.8% and 95.3%, P ≤ 0.001 over basal values, respectively). These results suggest that STX alters AAn_t. It is produced at least in part, because STX blocks voltage-gated sodium channels and this blockade could decrease AAn_t release by exocytotic dependent mechanism of depolarization.     

Effects of zinc pre-treatment on blood glutathione,serum zinc and kidney histological organisation in male rats exposed to cadmium

The effects of sub-chronic exposure to cadmium (Cd) on the blood glutathione, serum zinc and on the kidney histological organisation in rats as well as the possible protective role of zinc (Zn) are the object of this study. For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl₂, administered in five doses (each of 0.4 mg Cd/kg b.w.) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg b.w., i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl₂, administered in doses of 0.8 mg Zn/kg b.w., giving a total dose of 4 mg Zn/kg b w, i.p.; a control group received 0.5 mL of physiological saline in an identical manner. Intoxication with Cd was followed by a significant decrease in blood glutathione, increase in oxidized glutathione as well as histological damage in kidneys. Pre-treatment with Zn exhibited a protective role against Cd toxicity with a significant decrease in serum zinc content. This fact may be explained by an excessive use of zinc in metallothionein synthesis as a cadmium detoxification agent.     

Evaluation of the adverse effects of two commonly used fertilizers,DAP and urea,on motility and orientation of the green flagellate Euglena gracilis

The effect of two commonly used fertilizers, DAP (diammonium phosphate) and urea was studied on the freshwater flagellate Euglena gracilis using the automatic biotest ECOTOX. NOEC and EC₅₀ values for various parameters like motility, velocity, cell shape and gravitaxis were calculated. The NOEC and EC₅₀ values obtained for DAP were much lower than those for urea; i.e. DAP showed a stronger inhibitory effect as compared to urea. The inhibition caused by DAP increased with increasing exposure time over 24 h but urea showed no augmentation with increasing exposure time. Application of DAP resulted in an increased pH and high concentrations of ammonia but urea did neither affect the pH nor affect the ammonia concentration. Recovery experiments in deionized water after urea application showed a reconstitution of motility after 72 h. After an application of 1.35 g L⁻¹ (24 h EC₅₀ for motility) DAP motility recovered after 72 h but motility did not recover when the concentration was doubled (2.7 g L⁻¹). The EC₅₀ values obtained were compared with the EC₅₀/LC₅₀ values reported for other aquatic organisms and were found to be comparable with the reported values.     

Histopathological and biological studies of the effect of cadmium on Rhinella arenarum gonads

This study was to determine the lethal dose 50 (LD₅₀) of CdCl₂ in adult Rhinella arenarum and analyzed the effect of two sublethal doses (0.5 and 5 mg/kg) of the xenobiotic in gonads. The 48 h LD₅₀ were 50.0 and 49.8 mg/kg for males and females respectively. Alterations in the ovary were evidenced by nuclear pleomorphism and cytoplasmic vacuolization of the oocytes at the early stages of development with the highest dose and an increase in the population of atretic oocytes. In the interstitial tissue we noticed congestion, edema and fibroblast proliferation. The nuclear maturation of the oocytes was affected by the xenobiotic in a dose- and time-dependent manner. In males, treatment with 5 mg/kg of cadmium (Cd) caused a decrease in the concentration, viability and straight progressive motility of sperm while there was an increase in immotile sperm. Testis histopathology revealed dilated seminiferous tubules, disappearance of cysts, tissue disorganization and leukocyte infiltration. Numerous germ cells showed hydropic tumefaction or signs of focal necrosis. The Cd content in animals intoxicated gonads with the highest sublethal dose was significantly higher than in the control. Results indicate that R. arenarum gonads are target for the xenobiotic, compromising the formation of gametes competent for fertilization, the effective CdCl₂ dose being 5 mg/kg.     

Toxicokinetics and toxicological effects of single oral dose of fumonisin B1 containing Fusarium verticillioides culture material in weaned piglets

Toxicokinetics and the toxicological effects of culture material containing fumonisin B₁ (FB₁) were studied in male weaned piglets by clinical, pathological, biochemical and sphingolipid analyses. The animals received a single oral dose of 5 mg FB₁/kg of body weight, obtained from Fusarium verticillioides culture material. FB₁ was detected by HPLC in plasma collected at 1-h intervals up to 6 h and at 12-h intervals up to 96 h. FB₁ eliminated in feces and urine was quantified over a 96-h period and in liver samples collected 96 h post-intoxication. Blood samples were obtained at the beginning and end of the experiment to determine serum enzyme activity, total bilirubin, cholesterol, sphinganine (Sa), sphingosine (So) and the Sa/So ratio. FB₁ was detected in plasma between 30 min and 36 h after administration. The highest concentration of FB₁ was observed after 2 h, with a mean concentration of 282 μg/ml. Only 0.93% of the total FB₁ was detected in urine between 75 min and 41 h after administration, the highest mean concentration (561 μg/ml) was observed during the interval after 8 at 24 h. Approximately 76.5% of FB₁ was detected in feces eliminated between 8 and 84 h after administration, with the highest levels observed between 8 and 24 h. Considering the biochemical parameters, a significant increase only occurred in cholesterol, alkaline phosphatase and aspartate aminotransferase activities. In plasma and urine, the highest Sa and Sa/So ratios were obtained at 12 and 48 h, respectively.     

Cadmium chronotoxicity at pituitary level: effects on plasma ACTH,GH, and TSH daily pattern

Cadmium is an endocrine disruptor that has been shown to induce chronotoxic effects. The present study was designed to evaluate the possible cadmium effects on the daily secretory pattern of adrenocorticotropin hormone (ACTH), growth hormone (GH), and thyroid-stimulating hormone (TSH) in adult male Sprague-Dawley rats. For this purpose, animals were treated with cadmium at two different doses [25 and 50 mg/l cadmium chloride (CdCl₂)] in the drinking water for 30 days. Control age-matched rats received cadmium-free water. After the treatment, rats were killed at six different time intervals throughout a 24-h cycle. Cadmium exposure modified the 24-h pattern of plasma ACTH and GH levels, as the peak of ACTH content between 12:00 and 16:00 h in controls appeared at 12:00 h in the group treated with the lowest dose used, while it appeared between 16:00 and 20:00 h in rats exposed to 50 mg/l CdCl₂. In addition, the peak of GH content found at 04:00 h in controls moved to 16:00 h in rats exposed to 25 mg/l CdCl₂, and the highest dose used abolished 24-h changes of GH secretion. The metal treatment did not modify ACTH secretory pattern. Exposure to cadmium also increased ACTH and TSH medium levels around the clock with both doses used. These results suggest that cadmium modifies ACTH and TSH medium levels around the clock, as well as disrupted ACTH and GH secretory pattern, thus confirming the metal chronotoxicity at pituitary level.     

Effect of aging on 24-hour changes in dopamine and serotonin turnover and amino acid and somatostatin contents of rat corpus striatum

This study examined the 24-hour changes in a number of transmitters in the corpus striatum of young and middle-aged male Wistar rats. The contents of excitatory amino acids (glutamate, aspartate) and inhibitory amino acids (gamma-aminobutyric acid, GABA; taurine, glycine) and of somatostatin were measured in 2-month- and 18- to 20-month-old rats killed at six different time points along the 24-hour cycle. The striatal serotonin and dopamine turnover was also measured. Both young and middle-aged rats showed significant 24-hour variations in striatal glutamate and aspartate contents; only in young rats these variations fitted a cosine function, with acrophase during the first part of rest span. Mesor values of striatal excitatory amino acid contents were lowest in middle-aged rats. Significant 24-hour variations in striatal contents of GABA, taurine, and glycine occurred in young rats, while only striatal GABA exhibited 24-hour changes in middle- aged rats (acrophases during the first part of rest span). For every inhibitory transmitter, the mesor values in middle-aged rats were significantly lower than in young rats. The 24-hour variation of the striatal somatostatin content showed acrophase during the first part of rest span, mesor values and amplitude being lowest in middle-aged rats. Aging rats exhibited significantly higher mesor values of striatal serotonin turnover (34% increase) and lower mesor values of dopamine turnover (69% decrease) than their younger counterparts. Some of the circadian modifications of motor function seen in aging rats could be related to the striatal transmitter changes reported herein.     

Comparative assessment of in situ bioremediation potential of cadmium resistant acidophilic Pseudomonas putida 62BN and alkalophilic Pseudomonas monteilli 97AN strains on soybean

A study was undertaken to examine the effects of the acidophilic strain 62BN (pH 5.5) and alkalophilic strain 97AN (pH 9.0) on remediation of cadmium and their subsequent effects on soybean (Glycine max var. PS-1347) in acidic and alkaline soils, respectively. The effect of cadmium on soybean plants was studied in acidic (pH 6.3 ± 0.2) and alkaline (8.5 ± 0.2) soil amended with 124 μM CdCl₂ concentration, respectively, and the cadmium toxicity was evident from stunted growth, poor rooting, and cadmium accumulation in each case. Furthermore, 16S ribosomal DNA (rDNA) sequencing identified 62BN as a Pseudomonas putida strain and 97AN as a Pseudomonas monteilli strain. In situ studies showed that on seed bacterization, both the P. putida 62BN strain and P. monteilli 97AN strain were able to enhance plant growth in terms of agronomical parameters, in the presence of cadmium in acidic and alkaline soils, respectively. Apart from this, strain 62BN and 97AN reduced cadmium concentration in plant and soil significantly (p < 0.05) in their respective soil types. Further comparative analysis revealed that P. putida 62BN was more effective than P. monteilli 97AN strain in remediation of cadmium. The bacterial strains offer promise as inoculants to improve the growth of plants in the presence of toxic Cd concentrations in the environment with their optimum pH.     

AhpC (alkyl hydroperoxide reductase) from Anabaena sp. PCC 7120 protects Escherichia coli from multiple abiotic stresses

Alkyl hydroperoxide reductase (AhpC) is known to detoxify peroxides and reactive sulfur species (RSS). However, the relationship between its expression and combating of abiotic stresses is still not clear. To investigate this relationship, the genes encoding the alkyl hydroperoxide reductase (ahpC) from Anabaena sp. PCC 7120 were introduced into E. coli using pGEX-5X-2 vector and their possible functions against heat, salt, carbofuron, cadmium, copper and UV-B were analyzed. The transformed E. coli cells registered significantly increase in growth than the control cells under temperature (47 °C), NaCl (6% w/v), carbofuron (0.025 mg ml^?1), CdCl₂ (4 mM), CuCl₂ (1 mM), and UV-B (10 min) exposure. Enhanced expression of ahpC gene as measured by semi-quantitative RT-PCR under aforementioned stresses at different time points demonstrated its role in offering tolerance against multiple abiotic stresses.     

Combined effects of temperature and cadmium on developmental parameters and biomarker responses in zebrafish (Danio rerio) embryos

To determine the interactions between temperature and cadmium on zebrafish (Danio rerio) development, fertilized eggs were exposed to combinations of three temperature levels (21 °C, 26 °C, and 33 °C) and six cadmium concentrations (0, 0.25, 0.5, 2.0, 5.0, and 10.0 mg/L). Endpoints used included LC₅₀ value (48 h), developmental rate, mortality, heart rate, hatching success, liver histopathology, embryo abnormalities, and heat shock protein (hsp) induction. Results showed a significant acceleration in the developmental rate with increasing temperature and irrespective of the presence of cadmium. Data on LC₅₀ and ELS-test revealed that simultaneous exposure to both cadmium ions and cold stress (21 °C) was highly detrimental to growing embryos, causing a pronounced mortality and a significant reduction in average heart rate and embryo hatchability. In contrast, no similar reactions to cadmium were observed in pre-hatched embryos exposed to both control (26 °C) and high temperature (33 °C), and this can be explained by the significantly higher expression of hsp (hsp70) in embryos at these temperatures. Upon hatching, however, the larvae showed increased sensitivity to cadmium. The severity of malformations in the post-hatched larvae was in the order: hot cadmium stress>cold cadmium stress>cadmium stress alone>no stress at all. Liver histopathology as well as depletion in glycogen reserves exhibited greater severity with increasing cadmium concentration, irrespective of temperature. The present study confirms that temperature effectively confounds cadmium toxicity and needs to be considered for the accurate prediction and assessment of cadmium-induced toxicity in fish.     

Brain most susceptible to cadmium induced oxidative stress in mice

Accumulated evidence over the years indicate that cadmium (Cd) may be a possible etiological factor for neurodegenerative diseases. This may possibly be linked to excessive generation of free radicals that damages the organs in the body depending on their defence mechanism. Since Cd is a toxic agent that affect several cell types, the aim of this study was to shed light on the effect of Cd and its consequences on different organs of the mice body. To test the hypothesis of concentration dependent Reactive Oxygen Species (ROS) generation and DNA damage, observations were done in the serum of 4–5 weeks old male Swiss albino mice by treating with cadmium chloride (CdCl₂) in drinking water for 30 days. The expression of Bcl-2-associated X protein (Bax) an apoptotic marker protein was two times higher in brain compared to liver at an exposure level of 0.5 mg L⁻¹ CdCl₂. Furthermore the correlation and linkage data analysis of antioxidant defence system revealed a rapid alteration in the brain, compared to any other organs considered in this study. We report that even at low dose of Cd, it impaired the brain due to lipid peroxidase sensitivity which favoured the Cd-induced oxidative injury in the brain.     

Possible recovery from an acute envenomation in male rats with LD50 of Echis coloratus crude venom: I-A seven days hematological follow-up study

The effect of an acute LD₅₀ dose of Echis coloratus crude venom in male albino rats was tested on blood parameters: white blood cells (WBCs), red blood cells (RBCs), platelets count, hemoglobin, hematocrit, mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC), also serum glucose, total protein, triglycerides with alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) enzyme activities. The effect of the LD₅₀ dose was monitored over a period of seven days, with time intervals of 1, 3, 6, 12, 24, 72 h. All of the tested parameters show fluctuations with time and with tendency to regain normal control level after 12 h. At 12–24 h it seems to be crucial for the process of physiological recovery, in spite of the irreversible damage and tissue distraction. The process of physiological adaptation and recovery from the lethal destructive venom effect seems to stabilize after one week, leaving the animal alive with several biochemical altered metabolisms and disturbed physiological profile.     

Zinc and N-acetylcysteine modify mercury distribution and promote increase in hepatic metallothionein levels

This study investigated the ability of zinc (Zn) and N-acetylcysteine (NAC) in preventing the biochemical alterations caused by mercury (Hg) and the retention of this metal in different organs. Adult female rats received ZnCl₂ (27 mg/kg) and/or NAC (5 mg/kg) or saline (0.9%) subcutaneously and after 24 h they received HgCl₂ (5 mg/kg) or saline (0.9%). Twenty-four hours after, they were sacrificed and analyses were performed. Hg inhibited hepatic, renal, and blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, decreased renal total thiol levels, as well as increased serum creatinine and urea levels and aspartate aminotransferase activity. HgCl₂-exposed groups presented an important retention of Hg in all the tissues analyzed. All pre-treatments demonstrated tendency in preventing hepatic δ-ALA-D inhibition, whereas only ZnCl₂ showed this effect on blood enzyme. Moreover, the combination of these compounds completely prevented liver and blood Hg retention. The exposure to Zn and Hg increased hepatic metallothionein levels. These results show that Zn and NAC presented promising effects against the toxicity caused by HgCl₂.     

Apple juice attenuates genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of rats

The aim of this study was to evaluate the health benefits associated with apple consumption following cadmium exposure. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (non-treated group, CTRL); cadmium group (Cd) and apple juice group (Cd + AJ). The results showed a decrease in the frequency micronucleated cells in bone marrow and hepatocytes in the group exposed to cadmium and treated with apple juice. Apple juice was also able to reduce the 8OHdG levels and to decrease genetic damage in liver and peripheral blood cells. Catalase (CAT) was decreased following apple juice intake. Taken together, our results demonstrate that apple juice seems to be able to prevent genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.     

Protective effect of taurine,glutathione and trehalose on the liquid storage of ram semen

Oxidative damage to sperm resulting from reactive oxygen species generated by the cellular components of semen during liquid storage is possibly one of the main causes for the decline in motility and fertility during storage—the other detrimental cause is low temperature on the destabilisation of sperm membrane structure. The aim of this study was to determine the effects of the addition of the anti-oxidants taurine and glutathione (GSH), and the membrane structure stabiliser, trehalose, on sperm viability during low temperature liquid storage. A total number of 36 ejaculates were collected using the artificial vagina from four Chios rams and nine replicates of the ejaculates were diluted with a Tris-based extender containing additives as the control. The sperm motility, percentage abnormal sperm, plasma membrane intact sperm and the hypo-osmotic swelling test (HOST) were determined during storage of semen at 5 °C for a period of 0, 6, 24 and 30 h of liquid storage, respectively. Trehalose at a level of 50 mM provided the best maintenance of motility at 6 and 30 h (P < 0.05), and gave the highest percentage (69.0 ± 2.0% and 64.6 ± 1.8%, respectively) of viable sperm at 24 and 30 h (P < 0.01). Trehalose treatment at a concentration of 50 mM also resulted in the highest percentage of membrane-intact sperm (53.7 ± 2.9%) after performing HOST at 30 h. The anti-oxidant treatments GSH 5–10 mM and taurine at 50 mM provided a significant improvement in sperm survival during the 6 h of liquid storage at 5 °C (P < 0.05). In conclusion, many aspects of sperm protection, e.g. sperm motility, viability and membrane stabilisation of the sperm cells during relative low temperature storage, are the key factors determining the preservation of sperm function. Future efforts toward improving function of ram sperm kept in low temperature storage should concentrate on anti-oxidant additives. The results of this study provide a new approach to the preservation of sperm from rams of the Chios and related breeds, and so contribute to the improvement of these breeds for the world sheep industry.     

Blood lead and cadmium levels in a six hospital employee population. PESA study, 2009

IntroductionExposure to lead and cadmium is a public health problem due to the broad exposure to these toxic substances among the general population. The objective of this study is to determine blood lead and cadmium concentrations in a working population drawn from six university hospitals in Madrid, Getafe, Cartagena, Santiago de Compostela, Santander and Palma de Mallorca (Spain) and to identify associated factors.Materials and methods951 individuals participated in the study and were administered the standardized PESA^® questionnaire regarding exposure to lead and cadmium. The blood lead and cadmium concentrations were measured by electrothermal atomization atomic absorption spectrometry with Zeeman background correction in Perkin-Elmer spectrometers, guaranteeing the transferability of the results.ResultsThe median overall blood lead concentration was: 1.6 μg/dL (IQR: 0.9–2.7) and that of cadmium was: 0.21 μg/L (IQR: 0.10–0.50). There were significant differences in lead levels between men (2 μg/dL) and women (1.5 μg/dL), postmenopausal (2.6 μg/dL) and premenopausal women (1.1 μg/dL), and between participants who cooked in earthenware (2.1 μg/dL) and those who did not (1.5 μg/dL). The median of cadmium in women (0.24 μg/L) was higher than in men (0.11 μg/L) and was also higher in subjects who smoked (0.70 μg/L) than in non-smokers (0.13 μg/L).ConclusionsA reduction in blood lead and cadmium levels was observed with respect to previous studies carried out in Spain. Nevertheless, the results suggest there are certain factors which increase risk such as age, gender, menopause, age of housing, cooking in lead-glazed earthenware and exposure to cigarette smoke.     

Intermittent cold-induced hippocampal oxidative stress is associated with changes in the plasma lipid composition and is modifiable by vitamins C and E in old rats

This study primarily investigated the effects of intermittent cold exposure (ICE) on oxidative stress (OS) in the hippocampus(HC) and plasma lipid profile of old male rats. Secondly, it evaluated structural changes in the hippocampus region of the rat’s brain. Thirdly, it attempted an evaluation of the effectiveness of the combined supplement of vitamins C and E in alleviating cold stress in terms of these biochemical parameters. Thirty male rats aged 24 months were divided into groups of five each: control (CON), cold-exposed at 10 °C (C10), cold-exposed at 5 °C (C5), supplemented control (CON+S), and supplemented cold-exposed at either 5 °C (C5+S) or 10 °C (C10+S). The rats were on a daily supplement of vitamin C and vitamin E. Cold exposure lasted 2 h/day for 4 weeks. Rats showed increased levels of hydrogen peroxide (H₂O₂), and thiobarbituric acid reactive substances (TBARS) in the HC at 10 °C with further increase at 5 °C. Cold also induced neuronal loss in the hippocampus with concomitant elevations in total cholesterol (TCH), triglycerides (TG) and low-density lipoproteins (LDL-C) levels, and a depletion in high-density lipoprotein (HDL-C). A notable feature was the hyperglycaemic effects of ICE and depleted levels of vitamins C and E in the hippocampus and plasma while supplementation increased their levels. More importantly, a positive correlation was observed between plasmatic LDL-C, TCH and TG and hippocampal TBARS and H₂O₂ levels. Further, intensity of cold emerged as a significant factor impacting the responses to vitamin C and E supplementation. These results suggest that cold-induced changes in the plasma lipid profile correlate with OS in the hippocampus, and that vitamin C and E together are effective in protecting from metabolic and possible cognitive consequences in the old under cold exposures.