Effects of maternal hypothyroxinemia on the expression of biochemical functions in the CNS of the adult rat

The importance of thyroid hormones in the development and maintenance of normal CNS functions, has long been well established. Iodine-deficient areas are scattered all over the world. Maternal hypothyroxinemia in early pregnancy, as a consequence of iodine deficiency, is associated with an increased incidence of neurological cretinism in the offspring. This condition is irreversible and is manifested in severe cases by mental retardation, deaf-mutism, diplegia of the inferior extremities, gait disorders and sometimes strabismus and stunted growth. In the adult, these conditions cannot be corrected by a normal thyroid state or replacement therapy, suggesting the existence of specific phases in early brain development during which correct exposure to thyroid hormones is of critical importance, and there is a possible fetal dependance on maternal thyroxine. However, the putative biochemical disorders associated with latter have not been studied in detail. The aim of the study was thus to evaluate the biochemical changes in different brain regions due to maternal hypothyroxinemia in an animal model. Seven month old (adult) progeny born to normal and partially thyroidectomised rat dams were used. Total protein, protein profiles of cytosolic and particulate fractions, neuronal cell marker enzymes, myelin metabolic enzymes (oligodendroglial cell markers), and certain lipids were studied. Body weight, brain weight and protein concentrations of brain regions in experimental progeny were apparently unchanged. On the other hand protein profiles of both cytosolic and particulate fractions demonstrated significant alterations in some brain regions. Cytosolic protein bands of 25 kD and 38 kD were significantly changed in medulla, while a 31 kD protein band was absent in this brain region. A 97 kD and a 89 kD cytosolic protein bands were also changed respectively in cerebral cortex and paleocortex of TX dam progeny. A 79 kD protein band was the only particulate protein which significantly increased in medulla in the experimental progeny. Significant changes were observed in myelin metabolic enzymes in specific brain regions of experimental progeny, e.g. CNPase activity was decreased in medulla by 37% (p<0.05) and in midbrain by 32% (p<0.05), and 5'-nucleotidase activity was decreased significantly in the same regions by 33% (p<0.05) and 35% (p<0.05), respectively. In paleocortex, oleate esterase activity (a myelin metabolic enzyme) was significantly increased by 39% (p<0.05), whereas β-D glucuronidase activity (a neuronal marker) was significantly decreased by 30% (p<0.05), N-acetyl-β-D galactosaminidase activity (a general glial marker) was unchanged and the activity of sphingomyelinase was also unchanged in all brain regions studied. No change was observed in the concentration of cholesterol (a major component of the myelin lipid) in any brain region but other two specific myelin lipids, cerebroside and sulphatide demonstrated significant changes in experimental progeny. The former was decreased in medulla and the latter also decreased in the midbrain and paleocortex of progeny. Changes in myelin metabolic enzymes and lipids have suggested a deficit in myelin metabolism of adult progeny from partially thyroidectomised dam. In conclusion, these findings indicate that the effects of maternal hypothyroxinemia are brain region-specific. These effects are also irreversible, since they are observed in adult progeny and persist despite a normal thyroid state. It is well known that glial cell proliferation and acquisition in the rat occurs postnatally, when the thyroid is functionally active. It is argued that the thyroid hormone environment of the fetus, before the onset of an independent fetal hypothalamic-pituitary-thyroid axis may be of critical importance for the expression of glial functions after birth. It is suggested that maternal hypothyroxinemia in early pregnancy may cause irreversible brain region- specific biochemical changes in adult progeny and thyroid hormones in early pregnancy may have an epigenic effect on the function of the adult CNS

The effect of chronic administration of l-arginine on the learning and memory of estradiol-treated ovariectomized rats tested in the morris water maze

OBJECTIVE: The present study was carried out to evaluate the effect of L-arginine on the learning and memory of estradiol-treated ovariectomized (OVX) rats. METHODS: Forty-eight rats were divided into six groups: (1) sham, (2) OVX, (3) sham-Est, (4) OVX-Est, (5) sham-Est-LA, and (6) OVX-Est-LA. The animals of the sham-Est and OVX-Est groups were treated by weekly injection of estradiol valerate (2mg/kg). The sham-Est-LA and OVX-Est-LA groups were treated in the same manner but with an additional daily injection of L-arginine (200mg/kg). After eight weeks, animals of all groups were tested in the Morris water maze. The escape latency and path traveled to reach the platform were compared between groups. RESULTS: Time latency and path length in the OVX group were significantly higher than in the sham group (P<0.05). The OVX-Est group had a significantly shorter traveled path length and time latency compared to the OVX group (P<0.001). Time latency and path length in the sham-Est group was significantly higher than in the sham group (P<0.001). Time latency and path length in the OVX-Est-LA group were significantly higher than in the OVX-Est group. CONCLUSIONS: These results allow us to propose that chronic treatment with estradiol enhances the spatial learning and memory of OVX rats, and that long term L-arginine treatment attenuates the effects of improvement produced by estradiol in OVX rats

Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth

INTRODUCTION: Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO) in learning and memory has been widely investigated. METHODS: This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03% methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3. DISCUSSION: Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01). In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001), and the time spent by this group in the target quadrant (Q1) during the probe trial was significantly lower (P<0.001). There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05). CONCLUSION: These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s) remains to be elucidated

Luteolin Reduced the Traumatic Brain Injury-Induced Memory Impairments in Rats: Attenuating Oxidative Stress and Dark Neurons of Hippocampus

Traumatic Brain Injury (TBI) is generally recognized as a major risk factor for memory impairments and Alzheimer’s disease (AD). In this experimental study, our aim was to investigate the ameliorating effects of luteolin (LUT) on the memory impairments, oxidative stress, and histopathological changes induced by TBI in rats. The adult male Wistar rats were randomly divided into six groups including: Control (Co), sham, TBI, TBI+LUT (10 mg/kg), TBI +LUT (25 mg/kg), TBI +LUT (50 mg/kg). To evaluate the protective effects of LUT on the memory of the rats, passive avoidance test using shuttle box was performed. Finally, the animals were anesthetized, and the brain tissues were removed and analyzed for oxidative stress parameters. Using histological methods, dark neuron production was also evaluated. There was a significant decrease in the latency time to enter the dark compartment in passive avoidance test in TBI animals. This latency time was significantly increased in TBI+LUT (25 mg/kg) and TBI+LUT (50 mg/kg) groups along with significant increases in superoxide dismutase and catalase activity in the hippocampal zone and a decrease in malondialdehyde (MDA). The number of dark neurons in the hippocampus decreased with all three doses of LUT. In the present study, LUT showed neuroprotective effects, improvement in learning and reduction in memory impairment induced by TBI in rats. Protection against oxidative stress might be a possible mechanism behind these effects. Further works are necessary to work out if LUT is potentially a suitable therapeutic candidate for neural disorders

The Effects of Hydroalcoholic Extract of Nigella sativa Seeds on Serum Estradiol and Prolactin Levels and obstetric Criteria due to Hypothyroidism in Rat

Background: The aim of this study was investigation of the effects of Nigella sativa (NS) seeds on hypothyroid pregnant rats and their progenies. Materials and Methods: Hypothyroidism was induced by propylthiouracil (PTU) 0.03% in drinking water. Female rats were divided into seven groups: control, PTU, PTU-NS (100, 200, and 400 mg/kg), and NS (100 and 400 mg/kg). All treatments were done 20 days before mating and during pregnancy. The weight of rat dams and progenies, number of progenies and serum T4, estradiol and prolactin (PRL) levels in rat dams were measured for all groups. Results: Serum T4 in all PTU-NS groups before mating was significantly increased versus PTU group. Body weight of rat dams before mating in all groups of PTU-NS was increased versus PTU group by P < 0.001, P < 0.05, and P < 0.001, respectively and in NS 100 and NS 400 was increased versus control group (P < 0.001). The number of offspring was significantly decreased in PTU and PTU-NS versus control group. The weight of progenies in NS 400 was higher than control group (P < 0.001) and was increased in PTU-NS 200 and PTU-NS 400 versus PTU group by P < 0.001 and P < 0.05, respectively. Serum PRL level in rat dams in control, PTU, and PTU-NS groups were not statistically different between groups but significantly increased in NS 400 group when compared to control group. Estradiol levels were not significantly different in rat dams at 5 days after delivery. Conclusion: These results demonstrated that feeding of rat dams with NS extract before mating has positive protective effects on progenies. These effects may be due to antioxidant properties of NS in reducing oxidative stress and thyroid damages induced by PTU

Renal injury, nephrolithiasis and Nigella sativa: A mini review

Objective: The incidence and prevalence of kidney stone is increasing worldwide. After the first recurrence the risk of subsequent relapses is higher and the time period between relapses is shortened. Urinary stones can be severely painful and make a huge economic burden. The stone disease may increase the vulnerability of patients to other diseases such as renal failure. Medicinal herbs are rich sources of antioxidants which are increasingly consumed globally for their safety, efficacy and low price. Nigella sativa is a spice plant that is widely used for prevention and treatment of many ailments in Muslim countries and worldwide. This review aims at investigation of the effects of Nigella sativa on renal injury and stone formation. Materials and Method: The scientific resources including PubMed, Scopus, and Google scholar were searched using key words such as: nephrolithiasis, urolithiasis, kidney/renal stone, renal injury, renal failure, urinary retention and black seed, black cumin, Nigella sativa and thymoquinone.    Results: N. sativa and its main component, thymoquinone showed positive effects in prevention or curing kidney stones and renal failure through various mechanism such as antioxidative, anti-inflammatory, anti-eicosanoid and immunomodulatory effects. The putative candidate in many cases has been claimed to be thymoquinone but it seems that at least in part, particularly in kidney stones, the herbal melanin plays a role which requires further investigation to prove. Conclusion: N. sativa and its components are beneficial in prevention and curing of renal diseases including nephrolithiasis and renal damages

Hypothyroidism and Ramadan fasting

Introduction: Fasting during the holy month of Ramadan is an obligation for all adult, healthy Muslims. As several studies have indicated, both fasting and energy restriction can alter thyroid hormone metabolism and affect the clinical features and well-being of hypothyroid patients. Hypothyroidism is more prevalent among women and the elderly. Its prevalence has been reported to be 4-8% of the general population. Despite the large body of animal research on fasting, few human studies have focused on Ramadan fasting and its impacts on hypothyroid patients. Materials & Methods: PubMed and Google scholar databases were searched using keywords such as Ramadan, fasting, hypothyroidism, and food restriction. Animal and human studies, which were highly relevant to the topic, were selected. Results: Four animal and 7 human studies were included in this article. We found that levothyroxine dosage should be increased for hypothyroid patients from the beginning of the month until 15-20 days after the end of Ramadan. Discussion: Fasting can change the concentration of thyroid hormones, thyroid-stimulating hormone level, and the associated metabolisms both in animals and humans. As the results indicated, hypothyroid individuals, who fast during the month of Ramadan, particularly women and the elderly, may suffer from thyroid hormone changes. For these patients, levothyroxine dosage should be increased to 25-50 µg/per day from the beginning of Ramadan until 15-20 days after the end of this month. Conclusion: An increased dose of levothyroxine during Ramadan is recommended for hypothyroid patients, particularly women and the elderly

Reduction of serum cholesterol in hypercholesterolemic rats by Guar gum

Objective: Several diseases are reported to be uncommon in those parts of the world where dietary fiber intakes are high, therefore, in this study; we evaluated the hypocholesterolemiceffects of a dietary fiber (guar gum) in hypercholesteromic rats. Materials and Methods: Rats were fed high-fat or a normal fed diet for 12-week then treated with 5% guar gum in their regime during a 28 days period. Results: Total cholesterol was significantly increased in high-fat diet rats, while administration of guar gum significantly lowered it. Body weight was significantly increased in high-fat diet rats while, at the end of 4-weeks treatment of guar gum, body weight of treated rats was significantly decreased. Conclusion: These results suggested that guar gum may be effective as hypocholesterolemic agent and may prevent hypercholesteromia in hypercholesteromic rats. The results also suggested that guar gum may be important for reducing body weight in hyperlipidemic rats