Melatonin ameliorates hemorrhagic shock-induced organ damage in rats

Hemorrhagic shock (HS) followed by resuscitation can result in production of several inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), leading to multiple organ dysfunction. Melatonin can attenuate organ damage with its anti-inflammation effects. The present study was designed to investigate the effects of melatonin on the physiopathology and cytokine levels after HS in rats.

HS was induced in rats by withdrawing 40% of the total blood volume (6 mL/100 gm body weight) from a femoral artery catheter, immediately followed by intravenous injection of 10mg/kg melatonin. Mean arterial pressure and heart rate were monitored continuously for 48 h after the start of blood withdrawal. Biochemical parameters, including levels of hemoglobulin, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and lactate, were determined 30 min before and 0, 1, 3, 6, 12, 24, and 48 h after induction of HS while an equal volume of normal saline was replaced as fluid resuscitation. Cytokine levels including TNF-α and IL-6 in the serum were measured at 1, 24, and 48 h after HS. The kidney, liver, lung, and small intestine were removed for pathology assessment at 48 h after HS.

HS significantly increased the heart rate, blood GOT, GPT, BUN, Cre, LDH, CPK, lactate, TNF-α, and IL-6 levels, and decreased hemoglobulin and mean arterial pressure in rats. Treatment with melatonin preserved the mean arterial pressure, decreased tachycardia, and markers of organ injury, and suppressed the release of TNF-α and IL-6, with no change in hemoglobulin after HS in rats.

Treatment with melatonin suppresses the release of serum TNF-α and IL-6, and decreases the levels of markers of organ injury associated with HS, thus ameliorating HS-induced organ damage in rats.