Melatonin and Bacterial Cellulose Regulate the Expression of Inflammatory Cytokines, VEGF, PCNA, and Collagen in Cutaneous Wound Healing in Diabetic Rats.

The poor healing of diabetic wounds is characterized by prolonged inflammation and decreased collagen deposition. Diabetic patients exhibit changes in the plasma concentrations of pro-inflammatory cytokines, and the role of specific dressings may have an impact on healing. This study aims to evaluate the effects of a combined treatment comprising a bacterial cellulose dressing and melatonin application on the regulation and expression of inflammatory cytokines, VEGF, PCNA, and collagen in the healing of cutaneous wounds of diabetic rats. Pro-inflammatory cytokines, including IL-6, TNF-α, and VEGF, along with PCNA and type I and III collagen, were evaluated after 14 days. Immunohistochemistry showed decreased levels of IL-6, TNF-α, and VEGF, along with an increased expression of PCNA and type I collagen, in the groups treated exclusively with melatonin and bacterial cellulose associated with melatonin compared to the control and the commercial healing agent. It was concluded that treating the skin lesions of diabetic animals supplemented with melatonin using a bacterial cellulose-based dressing has positive effects in regulating the expression of inflammatory cytokines, vascular endothelial growth factor, and collagen, showing that this association could be a viable therapy approach in wound healing.

Bacillus thuringiensis affects reproductive capacity of adult rat offspring.

We investigated the effects of B. thuringiensis-based biological insecticides, XenTari and Dipel, and deltamethrin on the reproductive development of pups of pregnant rats. Twenty 90-day-old pregnant rats were divided randomly onto four equal groups: control group (GC) administered only water; XenTari group (GX) administered 1 mg XenTari (containing Cry1Ac toxin of B. thuringiensis)/100 g body weight; Dipel group (GDi) administered 1 mg Dipel (containing Cry1Aa, Cry1Ab and Cry1Ac toxins of B. thuringiensis)/100 g body weight; and a deltamethrin group (GDe) administered 2 mg deltamethrin (0.08 ml Keshet 25EC)/kg body weight as a positive control. Insecticides were administered by gavage at doses of 1 mg/100 g/day (GX and GDi), and 2 mg/kg/day (GDe) during pregnancy and lactation. Treatment with both biologic and synthetic insecticides reduced the weight gain of the mothers. The biological insecticides reduced the number, weight and length, and increased malformation and mortality of the offspring. In female offspring for all three groups administered insecticides, opening of the vagina was delayed, metestrus was increased and estrogen and progesterone levels were reduced compared to proestrus, estrus and metestrus of the cycle. The ovaries of female offspring of all three groups administered insecticides contained numerous tertiary and atretic follicles, few corpora lutea, primary and secondary follicles, and reduced estrogen receptors compared to controls. In male offspring, all three groups exposed to insecticides exhibited reduced testosterone levels. Histopathological changes in the testes including vacuolation and desquamation of the seminiferous epithelium were observed only in the GX and GDi groups. The number of androgen receptors was reduced significantly in the testes and testicular morphometry revealed reduced tubule diameter, height of the seminiferous epithelium and total tubule length compared to the control. The biological insecticides, XenTari and Dipel, administered in sublethal doses to pregnant rats, caused reproductive changes in the offspring similar to those of the insecticide, deltamethrin.

Melatonin Administration Prevents Placental and Fetal Changes Induced by Gestational Diabetes.

Gestational diabetes mellitus (GDM) promotes changes in the placenta and fetuses, due to oxidative stress. Antioxidants can reduce oxidative stress in the placenta. We tested the hypothesis that melatonin (Mel) can prevent these effects in the placenta and fetuses, analyzing their histology, histochemistry, morphometry, and immunohistochemistry. Thirty albino rats were used, divided into groups: CG-pregnant non-diabetic rats; GD-pregnant diabetic rats; GD + Mel-pregnant diabetic rats treated with melatonin. Diabetes was induced by streptozotocin at a dosage of 50 mg/kg i.p. Melatonin was administered in daily injections of 0.8 mg/kg i.p. Melatonin prevented the placental weight and fetal weight and length from increasing, in addition to histomoformetric, histochemical, and immunohistochemical changes in the placentas, compared to the placentas of diabetic females (GD). Thus, we conclude that melatonin has a great potential to prevent placental changes due to GDM.

Immunohistochemical and histophysiological study of prolonged use of nandrolone on reproductive organs and fertility.

We investigated possible changes in morphology and immunohistochemistry of the uterus and ovaries of rats caused by nandrolone (ND); we also investigated effects on fertility. We used 30 rats divided into three experimental groups: control (C), control vehicle (CV) and 5 mg/kg ND. Rats treated with ND exhibited loss of estrous cyclicity with predominance of the estrus phase, increased body weight and an organosomatic index that was decreased for the ovaries, but increased for the uterus. In the ovary, we observed a reduction in primary and secondary follicles and an increase in tertiary follicles; no corpora lutea were observed. Estrogen and progesterone levels were reduced. In the uterus, the endometrium was edematous with hyperplasic glands. The cytokines, TNFα and IL6, and the apoptotic index were increased in rats treated with ND. VEGF-A was increased in the ovaries and decreased in the uterus. We conclude that ND disrupts ovarian and uterine histophysiology by establishing an anovulatory and inflammatory condition, which directly affects reproduction.

Protective action of melatonin on diabetic rat testis at cellular, hormonal and immunohistochemical levels.

The aim of the present study was to analyze the effects of melatonin treatment on diabetic rat testes. Fifty albino rats were divided into the following groups: CG: control group; GD: placebo-induced and placebo-treated mice; GDI: insulin-induced and post-confirmation diabetes-induced rats; GDM: diabetes-induced and melatonin-treated post-confirmation mice and GDMS: diabetes-induced and melatonin-treated mice simultaneously. Melatonin was administered at a dose of 10 mg/kg in drinking water every day for 20 days at night. Diabetes was induced by streptozotocin (60 mg/kg) and confirmed after the fifth day of induction. Insulin was administered at 5 IU (international units)/day at different times of the day for 20 days. The testes were submitted to histopathological, morphometric, immunohistochemical and oxidative stress analysis. Melatonin moderately decreased glycemic levels, protected weight loss and morphometric changes in the testicles, increased antioxidant enzyme levels and stabilized plasma testosterone and androgen receptor levels and decreased inflammatory markers in the testicles. Showing its potential to mitigate diabetes effects.