The response of pre-inflammatory cytokines factors to different exercises (endurance, resistance, concurrent) in overweight men

Applying several energy systems and concurrent performing of various training models have a more effective role in preventing precocious occurrence of many diseases compared to training single energy system. This can be seen in case of physiologic and metabolic adaptations of the human body too. The present study attempted to investigate the effect of endurance, resistance and concurrent (endurance–resistance) training on pre-inflammatory cytokines in overweight men. Accordingly, 43 healthy overweight (BMI = 28.56± 2.67) young (23.7± 3.3 yr) students were volunteered to participate and randomly divided into three experimental (n= 11) and one control (n= 10) groups. The experimental groups performed 3 days/wk endurance, resistance and concurrent training for 8 weeks. Also, prior to and after the training, a blood sample was collected from the subjects in order to measure pre-inflammatory cytokines (IL-1b, IL-6 and TNF-a). Following 8 week training, repeated measure ANOVA results showed a significant difference in IL-1b (P =0.046) and IL-6 (P = 0.009) compared to baseline. However, this was not the case with the TNF-a. Furthermore, between group comparisons showed significant difference in IL-6 (P =0.020) between endurance and resistance groups. Within group comparisons (depended t student test) also showed a significant difference in IL-1b and IL-6 of endurance and concurrent groups compared to baseline. Generally, it can be concluded that endurance and concurrent exercise training in part has a positive effect on pre-inflammatory cytokines

In vivo and in vitro evaluation of the effects of Urtica dioica and swimming activity on diabetic factors and pancreatic beta cells

Abstract Background: Urtica dioica (UD) has been identified as a traditional herbal medicine. This study aimed to investigate the effect of UD extract and swimming activity on diabetic parameters through in vivo and in vitro experiments. Methods: Adult WKY male rats were randomly distributed in nine groups: intact control, diabetic control, diabetic + 625 mg/kg, 1.25 g/kg UD, diabetic + 100 mg/kg Metformin, diabetic + swimming, diabetic + swimming 625 mg/kg, 1.25 g/kg UD, and diabetic +100 mg/kg Metformin + swimming. The hearts of the animals were punctured, and blood samples were collected for biochemical analysis. The entire pancreas was exposed for histologic examination. The effect of UD on insulin secretion by RIN-5F cells in 6.25 or 12.5 mM glucose dose was examined. Glucose uptake by cultured L6 myotubes was determined. Results: The serum glucose concentration decreased, the insulin resistance and insulin sensitivity significantly increased in treated groups. These changes were more pronounced in the group that received UD extract and swimming training. Regeneration and less beta cell damage of Langerhans islets were observed in the treated groups. UD treatment increased insulin secretion in the RIN-5F cells and glucose uptake in the L6 myotubes cells. Conclusions: Swimming exercises accompanied by consuming UD aqueous extracts effectively improved diabetic parameters, repaired pancreatic tissues in streptozotocin-induced diabetics in vivo, and increased glucose uptake or insulin in UD-treated cells in vitro. Keywords: Diabetes, Urtica dioica, Insulin resistance, Cholesterol, TG, Pancreatic islet beta cells, Swimming exercis

The effects of sex-steroids and menstrual cycle/oestrous phases on knee ligament laxity in humans and rodents / Firouzeh Dehghan

The incidence of non-contact knee injury was reported higher in female than male. In female, the occurrence of this injury was related to different phases of the menstrual cycle. In view of this, we investigated the followings: (i) changes in knee laxity in rodent model under different sex-steroid influence; (ii) mechanisms underlying changes in knee laxity, which involves differential expression of relaxin receptors and (iii) correlation between knee laxity and serum levels of sex-steroids and relaxin at different phases of the menstrual cycle. In first part of the study, ovariectomized WKY rats were divided into different treatment groups (n=6 per group): different doses of 17 β-oestradiol, progesterone and testosterone were administered. The hormones were injected subcutaneously for 3 consecutive days. In parallel, steroid hormone receptor blockers and enzyme inhibitor (ICI 182780, PHTPP, MPP, Mifepristone, Flutamide, and Finasteride) were also injected with the respective agonist. In parallel, intact rats were grouped based on their oestrous cycle stages: proestrus, estrus, metestrus and diestrus. In ovariectomized steroid treated and intact rats, knee range of motion (ROM) was measured by using a digital miniature goniometer. The rats were sacrificed and expression of relaxin receptor isoforms, RXFP1 and RXFP2 mRNAs and proteins in knee ligaments and tendons were determined. Meanwhile, in humans, changes in knee laxity were observed at different phases of the menstrual cycle in the female athletes. The knee varus and valgus angles were determined at different phases of the menstrual cycle by using an orthopedic goniometer ruler. Blood was withdrawn and serum levels of oestrogen, progesterone and relaxin were determined in human at different phases of their menstrual cycle. Our findings showed a significant increase in knee ROM in rats following oestrogen and progesterone treatment however was decreased following testosterone treatment. Changes in knee ROM was antagonized by the concomitant administration of oestrogen, progesterone and androgen receptor antagonists. Knee ROM was high at proestrus and diestrus stages of the oestrous cycle. Progesterone and oestrogen up-regulated while testosterone down-regulated RXFP1 and RXFP2 mRNA and protein expressions which were antagonized by the respective steroid hormone antagonist. Meanwhile, relaxin administration increases knee ROM in oestrogen and progesterone treated but not testosterone treated groups indicating relaxin receptor up-regulation. In humans, significant difference in knee varus and valgus angles were observed in female athletes and non-athletes at different phases of the menstrual cycle which was the highest in the ovulatory and menstrual phases. Non-athletes have higher medial and lateral knee laxity as compared to athletes. This study has provided an insight into the mechanism underlying sex-steroid control of knee ROM via modulating the expression of RXFP1 and RXFP2 receptors. In rodents, increased RXFP1 and RXFP2 expressions could contribute to increase in knee laxity. In humans, the increase in laxity at ovulatory and mid-luteal phases of the cycle was consistent with high level of oestrogen and progesterone. In both intact rats and humans, strong correlations was noted between knee laxity and serum relaxin levels. Our study has provided the basis underlying female susceptibility towards non-traumatic knee injury at different phases of their reproductive cycle

Testosterone Reduces Knee Passive Range of Motion and Expression of Relaxin Receptor Isoforms via 5α-Dihydrotestosterone and Androgen Receptor Binding

Ovarian steroids such as estrogen and progesterone have been reported to influence knee laxity. The effect of testosterone, however, remains unknown. This study investigated the effect of testosterone on the knee range of motion (ROM) and the molecular mechanisms that might involve changes in the expression of relaxin receptor isoforms, Rxfp1 and Rxfp2 in the patella tendon and lateral collateral ligament of the female rat knee. Ovariectomized adult female Wistar rats received three days treatment with peanut oil (control), testosterone (125 and 250 μg/kg) and testosterone (125 and 250 μg/kg) plus flutamide, an androgen receptor blocker or finasteride, a 5α-reductase inhibitor. Duplicate groups received similar treatment however in the presence of relaxin (25 ng/kg). A day after the last drug injection, knee passive ROM was measured by using a digital miniature goniometer. Both tendon and ligament were harvested and then analysed for protein and mRNA expression for Rxfp1 and Rxfp2 respectively. Knee passive ROM, Rxfp1 and Rxfp2 expression were significantly reduced following treatment with testosterone. Flutamide or finasteride administration antagonized the testosterone effect. Concomitant administration of testosterone and relaxin did not result in a significant change in knee ROM as compared to testosterone only treatment; however this was significantly increased following flutamide or finasteride addition. Testosterone effect on knee passive ROM is likely mediated via dihydro-testosterone (DHT), and involves downregulation of Rxfp1 and Rxfp2 expression, which may provide the mechanism underlying testosterone-induced decrease in female knee laxity

Changes in Knee Laxity and Relaxin Receptor Isoforms Expression (RXFP1/RXFP2) in the Knee throughout Estrous Cycle Phases in Rodents.

The changes in knee laxity and relaxin receptor expression at different phases of rodent estrous cycle are not known. Here, changes in the parameter were investigated in rats at different phases of the estrous cycle. Estrous cycle phases of intact female rats were determined by cytological examination of the vaginal smear. Following phase identification, blood was collected for serum hormone analyses. Knee passive range of motion (ROM) was determined by using a digital miniature goniometer. The animals were then sacrificed and patellar tendon, collateral ligaments and hamstring muscles were harvested for relaxin/insulin-like family peptide receptor 1 and 2 (RXFP1/RXFP2) analyses. Knee passive ROM was the highest at proestrus followed by diestrus and the lowest at estrus. Estrogen level was the highest at proestrus while progesterone and relaxin levels were the highest at diestrus. A strong correlation was observed between relaxin and progesterone levels. At proestrus, expression of RXFP1 and RXFP2 proteins and mRNAs were the highest at proestrus followed by diestrus and estrus. The finding shows that higher level of progesterone and relaxin in diestrus might be responsible for higher laxity of knee joint in rats

Correlation coefficient of sex steroid and knee range of motion.

<p>Correlation coefficient of sex steroid and knee range of motion.</p

Blot analysis for validation of primary antibodies.

<p>A distinct band at ∼80 kDa, which is consistent with the molecular weight of one isoform of the RXFP1 receptor. A distinct band at ∼80 kDA is shown RXFP2 receptor, which is consistent with the molecular weight. Western blot target bands increased with increasing of sample concentration with same antibody concentration.</p

Mean serum hormone levels are presented as mean + SEM in intact female rats.

<p>*The level of oestrogen was the highest at proestrus (P<0.05). # The level of progesterone was the highest at diestrus and proestrus compare to estrus (P<0.05). $Meanwhile, relaxin level was the highest at diestrus compare to 3 other stages of estrous cycles (P<0.05). A strong positive correlation (r = 0.901 & p<001) was observed between serum progesterone and relaxin levels throughout the phases of the estrous cycle.</p

RXFP1& RXFP2 mRNA and protein expressions in the patellar tendon.

<p>The expression of <b>(A)</b> RXFP1 mRNA <b>(B)</b> RXFP2 mRNA and <b>(C)</b> ratio of RXFP1& RXFP2/ β-actin and Western blot bands of these proteins in the patellar tendon homogenates. The mRNA and protein expression were the highest at proestrus and diestrus phases. *p<0.05 as compared to estrus and metestrus for the respective isoforms. Ps-prosterous; Es-estrus; Ms; metestrus; Ds; diestrus. Data were expressed as mean ± SEM and n = 6 per study group.</p

RXFP1& RXFP2 mRNA and protein expression levels in the collateral ligament.

<p>The expression of <b>(A)</b> RXFP1 mRNA <b>(B)</b> RXFP2 mRNA and <b>(C)</b> RXFP1 & RXFP2/β-actin and Western blot bands in the collateral ligament homogenates. The expression of mRNA and protein were the highest at proestrus followed by diestrus. *p<0.05 as compared to estrus and metestrus for the respective isoforms. Ps-proestrus; Es- estrus; Ms; metestrus; Ds; diestrus. Data were expressed as mean ± SEM and n = 6 per study group.</p