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

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

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

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

Beneficial Effects of Selective Orexin-A Receptor Antagonist in 4-aminopyridine-induced Seizures in Male Rats

Background: Orexins are excitatory neuropeptides which stimulate the central regulatory pathways. Orexins increase the penicillin-induced epileptic activity in rats. Orexin-A increases in different types of seizures and its elevated level is the characteristic feature in the epileptic children during polysomnography. Recently, the orexin receptor blockage has been reported to increase seizure threshold in mice; however, effect of the selective orexin-A receptor antagonist (SB-334867) on 4-aminopyridine (4-AP)-induced seizures has not been investigated. Materials and Methods: We used the intraperitoneal injection of 4-AP to induce seizure in male rats. Under urethane anesthesia, SB-334867 (50 and 100 nmol) was injected stereotaxically into the ventral hippocampal commissure. Using video recording, the effects of SB-334867 on electroencephalogram and tonic–clonic convulsions were compared to those that received diazepam or dimethyl sulfoxide (DMSO). Results: SB-334867 significantly decreased the duration of spike trains compared to DMSO-treated rats (P < 0.001) and reduced the duration of convulsive seizures (P < 0.05). Seizure onset was increased significantly by SB-334867, 50 nmol, compared to DMSO (P < 0.05) and diazepam (P < 0.01) treated rats. Conclusion: Antagonism of orexin-A receptor by a low-dose SB-334867 showed protective effects in 4-AP-induced seizure-like activities in anesthetized rats

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

Rheum turkestanicum rhizomes possess anti-hypertriglyceridemic, but not hypoglycemic or hepatoprotective effect in experimental diabetes

Objective: Rheum turkestanicum (R. turkestanicum) rhizomes have been used in Iranain traditional medicine as an anti-diabetic agent. The purpose of the present investigation was to evaluate the anti-diabetic and antioxidant activities of R. turkestanicum rhizome extract in streptozotocin-induced diabetic rats.Materials and Methods: Diabetes was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin in male Wistar rats. Diabetic rats received the decoction extract of R. turkestanicum rhizomes at the doses of 200, 400 and 600 mg/kg daily by gavage for 3 weeks. Serum glucose and lipid levels were measured in all groups before diabetes induction and at the end of week 3. Oxidative stress was evaluated in the liver by measurement of malondialdehyde levels and total thiol concentration at the end of the experiment.Results: A significant increase in serum glucose and triglyceride levels was observed in diabetic rats, which was accompanied by increased malondialdehyde levels and decreased total thiol concentration in the liver after 3 weeks. Treatment of diabetic rats with R. turkestanicum rhizome extract at the doses of 200, 400 and 600 mg/kg over a 3-week period did not change serum glucose, hepatic malondialdehyde and total thiol levels in diabetic rats. However, treatment with R. turkestanicum extract significantly decreased serum triglyceride levels in a dose-dependent manner at the end of the experiment.Conclusion: R. turkestanicum rhizome extract possess anti-hypertriglyceridemic, but not hypoglycemic or hepatoprotective effect in diabetic rats. Therefore, R. turkestanicum rhizome should be consumed with more caution by diabetic patients

Antihyperglycemic and antihyperlipidemic effects of hydroalcoholic extract of Securigera securidaca seeds in streptozotocin-induced diabetic rats

Background: Hyperlipidemia is an associated complication of diabetes mellitus. Lowering of serum lipid levels seems to be associated with a decrease in the risk of vascular disease and related complications. The purpose of the current study was to evaluate the antihyperglycemic and antihyperlipidemic effects of the hydroalcoholic extract of Securigera securidaca seeds in streptozotocin-induced diabetic rats. Materials and Methods: Female Wistar rats were randomly divided into four groups as follows: Control, diabetic, and diabetic rats treated with the Securigera extract at doses of 100 and 200 mg/kg. The animals were rendered diabetic by a single intraperitoneal injection of 55 mg/kg streptozotocin. Diabetic rats received the Securigera extract daily in drinking water from the day on which diabetes was confirmed for 4 weeks. The levels of serum glucose and lipids were spectrophotometrically measured in all groups at weeks 0 (before diabetes induction), 2, and 4. Results: The results showed that there was a significant increase in serum glucose, triglycerides, total cholesterol, and low density lipoprotein (LDL)-cholesterol in streptozotocin-induced diabetic rats, accompanied by a decrease in high density lipoprotein (HDL)-cholesterol. Treatment of diabetic rats with S. securidaca seed extract at a dose of 200 mg/kg over a 4-week period significantly reduced the levels of serum glucose, total cholesterol, and LDL-cholesterol and increased the level of HDL-cholesterol, compared to diabetic untreated rats. Conclusions: Securigera extract at a dose of 200 mg/kg exhibited hypoglycemic and hypolipidemic activities in streptozotocin-diabetic rats during the 4-week treatment period. This provides a valid scientific basis for using it in the treatment of diabetes in Iranian folk medicine