The active constituent of black seed, thymoquinone, reversed non-alcoholic fatty liver associated with experimental hypothyroidism in rats.

PMID: 

Rom J Morphol Embryol. 2019 ;60(2):479-486. PMID: 31658321

Abstract Title: 

Thymoquinone reverses nonalcoholic fatty liver disease (NAFLD) associated with experimental hypothyroidism.

Abstract: 

OBJECTIVES: To assess the efficacy of thymoquinone (TQ), the most active constituent in Nigella sativa, which is a medicinal plant from the Ranunculaceae family, in restoring the normal liver structure after 6-propyl-2-thiouracil (PTU)-induced hypothyroidism and explore the mechanism behind this.MATERIALS AND METHODS: Hypothyroidism was induced in rats by injection of PTU [6 mg∕kg body weight (b.w.)] for six weeks. Twenty-four adult male Wistar rats were divided into four groups; the control, TQ-treated at the dose 400 mg∕kg b.w., untreated hypothyroidism and TQ-treated hypothyroid groups. Serum levels of thyroid hormones and antioxidant profile were measured. Real-time polymerase chain reaction was used to assess gene expression of catalase (CAT). Liver was histopathologically examined using routine and immunohistochemical techniques.RESULTS: Livers of rats with hypothyroidism displayed nonalcoholic fatty liver disease (NAFLD) in the form of steatosis as well as nonalcoholic steatohepatitis (NASH). Moreover, there was an intralobular inflammatory reaction associated with significant (p

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This review summarizes potential mechanisms of the biological effects on the human body.

PMID: 

Med Pr. 2001 ;52(2):101-6. PMID: 11761657

Abstract Title: 

[A study on the biological effects of exposure mobile-phone frequency EMF].

Abstract: 

Together with a growing number of cellular telephone users increases the interest in the effect of electromagnetic fields (EMF) emitted by them on live organisms. The surveys on subjective complaints of cellular telephone users carried out in Sweden, Norway, UK, USA, New Zealand and Australia showed that head ache is the major complain, and it is more pronounced with analogue than digital telephones. Apart from head ache, fatigue and general ill-being, muscular pains and nausea are reported. Human experimental studies reveal that EMF emitted by cellular telephones may be responsible for periodical increase in arterial blood pressure, changes in electric activity of the brain. However, no changes in secretion of cerebral pituitary hormones: adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), growth hormone, prolactin (PRL), lactogenic hormone (LH), follicle-stimulating hormone (FSH) and melatonine. The animal experimental studies indicated that exposure to EMF of the microwave frequency activates the endogenous opioid system in the brain, while the studies of the brain neurotransmitter activity have not produced univocal results, some of them showed decline, others increase in acetylcholinesterase activity. In vitro studies reveal that EMF even below maximum permissible levels may induce changes in the blood-brain permeability barrier and disorders in active transport of Na+, K+ ions and release of Ca++ ions by cellular membranes. The studies carried out thus far have not produced clear-cut results, but they indicate that EMF of the microwave frequency, including the frequency emitted by cellular telephones may be responsible for various measurable biological effects. It is essential to find out whether these effects may affect human health.

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Increase in thyroid cancer incidence cannot be attributed to better diagnostic procedures and the role of both ionizing and non-ionizing radiation should be further studied.

PMID: 

BMC Cancer. 2016 07 7 ;16:426. Epub 2016 Jul 7. PMID: 27388603

Abstract Title: 

Increasing incidence of thyroid cancer in the Nordic countries with main focus on Swedish data.

Abstract: 

BACKGROUND: Radiofrequency radiation in the frequency range 30 kHz-300 GHz was evaluated to be Group 2B, i.e. 'possibly' carcinogenic to humans, by the International Agency for Research on Cancer (IARC) at WHO in May 2011. Among the evaluated devices were mobile and cordless phones, since they emit radiofrequency electromagnetic fields (RF-EMF). In additionto the brain, another organ, the thyroid gland, also receives high exposure. The incidence of thyroid cancer is increasing in many countries, especially the papillary type that is the most radiosensitive type.METHODS: We used the Swedish Cancer Register to study the incidence of thyroid cancer during 1970-2013 using joinpoint regression analysis.RESULTS: In women, the incidence increased statistically significantly during the whole study period; average annual percentage change (AAPC) +1.19 % (95 % confidence interval (CI) +0.56, +1.83 %). Two joinpoints were detected, 1979 and 2001, with a high increase of the incidence during the last period 2001-2013 with an annual percentage change (APC) of +5.34 % (95 % CI +3.93, +6.77 %). AAPC for all men during 1970-2013 was +0.77 % (95 % CI -0.03, +1.58 %). One joinpoint was detected in 2005 with a statistically significant increase in incidence during 2005-2013; APC +7.56 % (95 % CI +3.34, +11.96 %). Based on NORDCAN data, there was a statistically significant increase in the incidence of thyroid cancer in the Nordic countries during the same time period. In both women and men a joinpoint was detected in 2006. The incidence increased during 2006-2013 in women; APC +6.16 % (95 % CI +3.94, +8.42 %) and in men; APC +6.84 % (95 % CI +3.69, +10.08 %), thus showing similar results as the Swedish Cancer Register. Analyses based on data from the Cancer Register showed that the increasing trend in Sweden was mainly caused by thyroid cancer of the papillary type.CONCLUSIONS: We postulate that the whole increase cannot be attributed to better diagnostic procedures. Increasing exposure to ionizing radiation, e.g. medical computed tomography (CT) scans, and to RF-EMF (non-ionizing radiation) should be further studied. The design of our study does not permit conclusions regarding causality.

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Hesperidin reduces adverse symptomatic intracerebral hemorrhage.

PMID: 

Neurol Sci. 2019 Sep 2. Epub 2019 Sep 2. PMID: 31478148

Abstract Title: 

Hesperidin reduces adverse symptomatic intracerebral hemorrhage by promoting TGF-β1 for treating ischemic stroke using tissue plasminogen activator.

Abstract: 

Treatment with recombinant tissue plasminogen activator (rt-PA) is the most effective therapeutic option against brain ischemic stroke at the present time. However, elevated incidence of symptomatic intracerebral hemorrhage (SIH) greatly hinders ideal treatment outcome of rt-PA. We sought to assess the impacts of hesperidin on SIH following rt-PA therapies. Patients with ischemic stroke were assigned into two groups in a random fashion, to receive either rt-PA + placebo (Pc) or rt-PA + hesperidin. Treatment outcome was evaluated 24 h after the initial reperfusion using the transcranial Doppler ultrasonography (TCD) and the NIH Stroke Scale (NIHSS). Further, serum concentrations of transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-2, and MMP-9 were examined. Following the initial administration, stroke patients continued to receive either daily Pc or daily hesperidin, and the treatment outcome after 7 days was examined using the TCD, NIHSS, Glasgow Outcome Scale (GOS), and the Modified Rankin Scale (MRS). Combined treatment of rt-PA with hesperidin yielded significant improvement of outcomes, as revealed by better TCD and NIHSS scores as well as decreased SIH incidences, which could be attributable to elevation of TGF-β1 and reduction in serum levels of both MMP-2 and MMP-9 caused by hesperidin. Follow-up hesperidin treatment for 7 consecutive days also markedly enhanced the recovery of strokepatients, as indicated by TCD, MRS, GOS, and NIHSS. Findings of the present study strongly suggested potential clinical application of hesperidin supplement in rt-PA therapies to reduce SIH and thereby improve the treatment outcomes of rt-PA in patients with ischemic stroke.

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Women with adult acne were signficantly more likely to have high levels of thyroid antibodies than healthy controls. Antibody-positive patients were also more likely to have a significant elevation of C-Reactive protein.

PMID: 

J Eur Acad Dermatol Venereol. 2012 Apr ;26(4):413-6. Epub 2011 Apr 27. PMID: 21521376

Abstract Title: 

Association of thyroid autoimmunity with acne in adult women.

Abstract: 

BACKGROUND: During the last decades an increase has been observed regarding acne in adults and especially women.OBJECTIVE: To evaluate the association between thyroid disorder and the presence of post-adolescent acne in adult women, comparing with healthy controls.METHODS: 107 adult women with post-adolescent acne and 60 healthy controls were included. Complete blood count and standard biochemical profile of C-Reactive Protein (CRP) and levels of thyroid hormones and antibodies [triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), free T3 (FT3), free T4 (FT4), antithyroglobulin antibodies (anti-TG) and anti-thyroid peroxidase antibodies (anti-TPO)] were determined in all subjects of both the acne and control groups. A thyroid ultrasound was also performed.RESULTS: There was a statistically significant difference (P=0.008) in the prevalence of positive anti-TG antibodies, with 25.2% of the acne group and 8.3% of the control group having elevated (>40 U/mL) anti-TG levels, respectively. Adult women with acne had a statistically significant increased relative risk to have high levels of anti-TG in comparison with healthy controls (odds ratio 3.89, P=0.011). This association was independent of age. Values for TSH, FT4, FT3, T4 and anti-TPO did not significantly differ between the two groups. No significant difference was found regarding the thyroid ultrasound findings. Although there was no significant difference between cases and controls regarding CRP levels, it is interesting that we observed a significant elevation in CRP in those acne patients who had positive antithyroglobulin antibodies.CONCLUSIONS: It is likely that thyroid autoimmunity might be more frequent in the adult acne patients and this should be kept in mind when screening women with post-adolescent acne.

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Isotretinoin, a widely prescribed anti-acne drug, significantly alters serum thyroid parameters.

PMID: 

J Dermatolog Treat. 2017 Mar ;28(2):141-144. Epub 2016 Aug 8. PMID: 27425198

Abstract Title: 

Evaluation of thyroid function tests of acne vulgaris patients treated with systemic isotretinoin.

Abstract: 

BACKGROUND: Isotretinoin is a systemic retinoid used to treat acne and it binds receptors which are the member of steroid-thyroid hormone superfamily. Certain types of retinoids may cause abnormalities in serum thyroid function tests (sTFTs) by suppressing thyroid stimulating hormone (TSH). However, it is uncertain whether systemic isotretinoin has any effect on sTFTs.OBJECTIVE: The aim of the study was to find out if there is any alteration in sTFTs of patients with acne vulgaris treated with systemic isotretinoin.METHODS: A total of 51 patients (male/female: 22/29) with severe acne vulgaris treated with a total dose of 120 mg/kg isotretinoin were included into the study prospectively. Serum free T3 (fT3), free T4 (fT4) and TSH levels were measured at baseline, 3rd and 6th months of treatment.RESULTS: Mean serum TSH levels at baseline, 3rd and 6th months of treatment were 1.57 ± 0.67, 2.07 ± 0.88 and 2.25 ± 0.86 uIU/mL, respectively. Mean serum TSH levels increased significantly following isotretinoin therapy (p 

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Hesperidin suppressed hepatic precancerous lesions via modulation of exophagy.

PMID: 

J Cell Biochem. 2019 Sep 6. Epub 2019 Sep 6. PMID: 31489981

Abstract Title: 

Hesperidin suppressed hepatic precancerous lesions via modulation of exophagy in rats.

Abstract: 

The enormous cost of modern medicines warrants alternative strategies for the better management of hepatocellular carcinoma. Recently, exosomes have been shown to relay the oncogenic information through the horizontal transfer of RNAs between the cells. In this study, we modulated exosomal production and autophagy (exophagy) by the administration of hesperidin and evaluated its effect on the development of hepatic precancerous lesion (HPC) in rats. Diethylnitrosamine and 2-acetylaminofluorene were used in vivo to induce HPC in rats. Rats were allocated into five groups: naïve, HPC, and three hesperidin treated (50, 100, and 200 mg/kg/d; orally) for 4 consecutive days per week for 16 weeks. Liver tissues and blood samples were collected for histopathological, immunohistochemical, and transmission electron microscope examinations, liver function, alfa-fetoproteinlevel, and isolation of exosomal and autophagy RNAs. Hesperidin administration showed hepato-protective effects and improved the microscopic hepatic features with a decrease in glutathione S-transferase placental precancerous foci and the abundance of exosomes in liver tissues. Hesperidin improved liver function with a significant decrease in alfa-fetoprotein levels. Hesperidin dose-dependently decreased exosomal RAB11A messsenger RNA and long noncoding RNA-RP11-583F2.2 along with the increase in exosomal miR-1298, involved in the exophagy process. In conclusion, hesperidin likely suppresses liver carcinogenesis in rat model via the modulation of exosomal secretion and autophagy.

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These findings suggest that hesperidin is a potential therapeutic agent for hepatic ischemia and reperfusion injury.

PMID: 

Transplant Proc. 2019 Oct ;51(8):2828-2832. Epub 2019 Sep 4. PMID: 31493917

Abstract Title: 

Hesperidin Ameliorates Hepatic Ischemia-Reperfusion Injury in Sprague-Dawley Rats.

Abstract: 

OBJECTIVE: Hepatic ischemia and reperfusion (I/R) is a destructive event associated with high rates of liver failure after liver transplantation. Hesperidin significantly contributes to the antioxidant defense system and has been reported to act as a powerful agent against superoxide and hydroxyl radicals. Our objective was to investigate the protective effect of hesperidin against hepatic IR injury in a rat model.METHODS: We fed Sprague-Dawley rats either hesperidin (100 mg/kg/d) or saline. One week later, ischemia was induced by clamping the rats' common hepatic artery and portal vein for 30 minutes. The rats were divided into 3 groups: 1. the sham operated group; 2. the I/R group; and 3. the I/R-hesperidin group.RESULTS: Compared to the sham group, the I/R group had higher expression of serum aspartate aminotransferase and serum alanine aminotransferase and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, nitric oxide, and albumin. Compared to the I/R group, the I/R-hesperidin group had higher expression of catalase, superoxide dismutase, antioxidant and nitric oxide and lower expression of serum aspartate aminotransferase and serum alanine aminotransferase.CONCLUSIONS: Our findings suggest that hesperidin is a potential therapeutic agent for hepatic I/R injury.

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Hesperidin is a potential therapeutic agent for acute ischemia-induced renal damage.

PMID: 

Transplant Proc. 2019 Oct ;51(8):2838-2841. Epub 2019 Sep 4. PMID: 31493919

Abstract Title: 

Hesperidin Shows Protective Effects on Renal Function in Ischemia-induced Acute Kidney Injury (Sprague-Dawley Rats).

Abstract: 

OBJECTIVE: Hesperidin is a well-known flavanone glycoside copiously found in sweet orange and lemon, which was recently reported to possess significant anti-inflammatory, analgesic, antifungal, antiviral, antioxidant, and anticancer activities. Ischemia-reperfusion (I/R) injury is a major problem after renal transplantation. Furthermore, inflammatory responses to I/R exacerbate the resultant renal injury. In the present study, we investigated whether hesperidin exhibits renoprotective effects against I/R-induced acute kidney injury in a rat model.METHODS: We fed Sprague-Dawley rats either hesperidin (100 mg/kg/d) or saline. One week later, ischemia was induced by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion. The rats were randomly divided into 3 groups, which were treated as follows: 1. the sham operated group; 2. the I/R group; 3. the I/R-hesperidin group RESULTS: Compared to the sham group, the I/R group had higher expression of blood urea nitrogen and serum creatinine and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidants, and nitric oxide. Compared to the I/R group, the I/R-hesperidin group had higher expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, and nitric oxide and lower expression of blood urea nitrogen and serum creatinine.CONCLUSIONS: Hesperidin improved acute renal I/R injury through its antioxidant effects. These findings suggest that hesperidin is a potential therapeutic agent for acute ischemia-induced renal damage.

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