Amanita phalloides species mushrooms containing alpha-amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models. In the in vivo protocol, resveratrol (30 mg/kg) was given simultaneously with α-AMA (α-AMA + SR) or 12 (α-AMA + 12R) or 24 (α-AMA + 24R) hr after α-AMA administration. Silibinin (5 mg/kg) (α-AMA + Sil) and normal saline (α-AMA + NS) were given simultaneously with α-AMA. We found that liver transaminase levels in α-AMA + SR and α-AMA + 12R groups and histomorphologic injury score in the α-AMA + SR, α-AMA + 12R, α-AMA + 24R and α-AMA + Sil groups were significantly lower than that of the α-AMA + NS group. Resveratrol decreased mononuclear cell infiltration, necrosis and active caspase-3 immunopositivity in the liver. In the in vitro protocol, the effects of resveratrol and silibinin were evaluated in a reduction in cell viability induced by α-AMA in THLE-2 and THLE-3 hepatocytes. Neither resveratrol nor silibinin was found to be effective in increasing cell viability decreased by α-AMA + NS. As a conclusion, resveratrol was found to be effective in α-AMA-induced hepatotoxicity with its anti-inflammatory properties in in vivo conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with Amanita phalloides type mushroom poisonings.

Erectile dysfunction (ED) is defined in relation to the metabolic syndrome (metS). Hydrogen sulphide (H S), a gasotransmitter, has been revealed to get involved in hypertension, insulin secretion and regulation of vascular tone especially in erectile physiology. This study aimed to investigate the effect of H S on metS-induced ED. Animals were divided into two groups as control and metS, which were fed with standard diet or 60% high-fructose diet for 10 weeks respectively. The metS model was evaluated with biochemical analyses, waist circumference/tibia length ratio and HOMA index. Penile hemodynamic parameters were evaluated by the measurement of intracavernous pressure/mean arterial pressure ratio during cavernous nerve stimulation in the presence and absence of intracavernous injection of NaHS (100 μg/50 μl) and its control 0.9%NaCl (50 μl) in both groups. H S levels were measured in penile tissues by methylene blue assay. H S levels were significantly decreased in the penile tissues of the metS group. Decreased intracavernous pressure/mean arterial pressure ratio improved after intracavernous administration of NaHS in the metS group. These results suggest the significant role of H S in the metS-induced erectile dysfunction that could be a new therapeutic target.

Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway.

Background Resistin is known as a potential mediator of obesity‐associated insulin resistance. The high resistin level disrupts nitric oxide (NO)‐mediated relaxation which is also important in erectile function. An antioxidant alkaloid, Boldine, is known as anti‐diabetic and protects endothelial functions. Objectives We aimed to investigate resistin expression in penile tissue in the presence of insulin resistance (IR) and the effect of Boldine treatment on erectile functions in the metabolic syndrome (MetS) rat model. Materials and methods Wistar rats were randomly divided into three groups: Control, MetS, and boldine treated MetS group. MetS parameters were assessed by serum triglycerides (TG), uric acid (UA), glucose, insulin levels, HOMA index, and waist circumference (WC)/tibia length (TL) ratio. To evaluate erectile functions, intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio was performed during cavernous nerve stimulation. Protein expressions of resistin, endothelial nitric oxide synthase (eNOS), p(S1177) eNOS, and insulin receptor‐β were evaluated by Western blotting. Results TG, glucose, insulin levels, weight, WC/TL ratio, HOMA index and resistin expression in penile tissue were significantly increased and ICP/MAP values, and p (S1177) eNOS expression in penile tissue were decreased in MetS group. Boldine treatment enhanced ICP/MAP values, insulin receptor‐β and p(S1177) eNOS expressions compared with the MetS group. Discussion and Conclusion MetS caused a deterioration in erectile function accompanied by an increase in resistin expression and a reduction in eNOS enzyme activation in the rat penile tissues. Boldine treatment resulted in an improvement in erectile function, independent of resistin expression.

Introduction Although premature ejaculation (PE) is the most common sexual dysfunction in young men, its true pathophysiology has not yet been clearly elucidated. Aim To investigate the quantitative changes that occurred in an ejaculation model induced by para-chloroamphetamine (PCA) after botulinum-A toxin injection into the bulbospongiosus (BS) muscle in rats. Methods A total of 21 male rats weighing 300 to 350 grams were used in the study. The animals were divided into 3 groups: control, 1 unit of botulinum-A toxin injected, and 5 units of botulinum-A toxin injected. The botulinum-A toxin was percutaneously injected into the BS muscle, and the experiment was carried out 96 hours (5 days) after the injection. Main Outcome Measure The seminal vesicle (SV) was cannulated, and the BS muscle was dissected and connected to an amplifier (Biopac; Goleta, CA) to record the pressure and electromyography measurement. The ejaculation parameters were obtained after the PCA injection. Results The ejaculation latency time of the group receiving 5 units of botulinum-A toxin was statistically significantly longer (1092 ± 657 seconds) compared to the control group (298 ± 81 seconds) and the group receiving 1 unit of botulinum-A toxin (439 ± 100 seconds) (P = .003). Furthermore, the BS EMG area under the curve values for the group receiving 5 units of botulinum-A toxin were significantly lower (7.4 ± 1.2 V/s × 10–4) than those of the control group (13.6 ± 4.0 V/s × 10–4) and the group receiving 1 unit of botulinum-A toxin (13.6 ± 5.0 V/s × 10–4) (P = .009). No statistically significant difference was found between the groups in terms of the basal SV pressure, number of SV phasic contractions, maximum amplitude of the SV phasic contraction, and intervals between the SV phasic contractions and the BS muscle contractions. Clinical Implications Botulinum-A toxin injection is a potential treatment option for PE and should be further investigated by future clinical studies. Strengths and Limitations Ease of administration and prolonged duration of botulinum-A toxin are advantages of the existing treatment options. The risk of anejaculation due to the dosage should be kept in mind. Conclusions Injection of botulinum-A toxin into the BS muscle in rats significantly delayed the ejaculation latency time and affected the expulsion phase.