الفهرس 
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Abstract
Acute kidney injury (AKI) is defined as a clinical syndrome characterized by a rapid decrease in renal function together with the accumulation of waste products such as urea.
AKI complicates 1–7% of all hospital admissions and 1–25% of intensive care unit admissions. Furthermore, AKI is known as an independent risk factor for mortality. AKI increases the risk of death by 10- to 15-fold and results in a mortality rate of 50%.
The kidneys are the major targets for the toxic effects of various chemical agents and thus drug-induced AKI is a frequent entity in clinical medicine. The incidence of nephrotoxic AKI is difficult to estimate due to variabilities of patient populations and criteria of AKI. However, nephrotoxicity has been reported to contribute to about 8–60% of hospital-acquired AKI cases.
The development, progression, and recovery of AKI are a complex and highly orchestrated pathophysiologic process that is regulated by a myriad of signaling pathways. Of many of these pathways, glycogen synthase kinase 3b (GSK3b) has emerged as the integration point and plays a crucial role in the pathogenesis of AKI. Lithium is a selective inhibitor for GSK3b
Our aim of this study was to study the potential use of lithium in the treatment of acute kidney injury in a rat model.
Our study was carried out on 42 Male Sprague–Daley rats. All the rats were at the age of 6-8 weeks old weighting between 150 and 250 gm at the beginning of the study.
Rats were classified into groups as follows: according to the treatment given to Rats: group I (n: 7): Rats were given cisplatin intra-peritoneal injection with a dose of 5mg/kg in day zero to induce AKI. group II (n: 7): Rats were given saline intraperitoneal injection the same dose like cisplatin in day zero. group III(n:7): Rats were given lithium chloride intraperitoneal injection with dose 80mg /kg (high dose lithium) in day zero to assess acute effect of high dose lithium on kidney. group IV(n:7) : Rats with cisplatin induced AKI were given lithium chloride with a dose of 80mg/kg (high dose) in day 3 to assess its effect on recovery of AKI.group V(n:7): Rats with cisplatin induced AKI were given lithium chloride with a dose of 40mg/kg (low dose) in day 3 to assess its effect on recovery of AKI. group VI(n:7): Rats with cisplatin-induced AKI were given saline with the same dose as high dose lithium in day 3 to compare its effect on recovery of AKI to the effect of lithium chloride with its two doses.
The results of our study revealed that a single intraperitoneal injection of cisplatin (5 mg/kg) in rat induced acute kidney injury. cisplatin injury resulted in elevation in serum creatinine and blood urea levels at day 3. By day 3, cisplatin-induced a typical pattern of acute tubular necrosis, characterized by epithelial simplification, vacuolization of proximal tubular epithelium, luminal ectasia, epithelial necrosis, sloughing of tubular cell into lumen, and loss of brush border.
Saline injection same dose like cisplatin and lithium chloride (80mg/kg) injection did not cause any elevation in serum creatinine and blood urea levels at day 3.
Histopathology of kidneys from rats treated alone with saline or lithium chloride (80 mg/kg) remained normal.
After day 3, serum creatinine and blood urea levels in cisplatin-injured rats continued to rise. The effect of lithium chloride treatment low dose (40 mg/kg) and high dose (80 mg/kg) on serum creatinine and blood urea levels showed significant regression in the rising of serum creatinine and blood urea in lithium chloride treated rats in comparison to saline-treated rats. serum creatinine 6.06 ± 0.72in saline group versus 3.15 ± 1.87in lithium chloride low dose group and4.06± 1.99 in lithium chloride high dose group. Blood urea407.84 ± 171.59 in saline group versus184.57 ± 127.15 in lithium chloride low dose group and 128.88 ± 76.06 in lithium chloride high dose group signifying an accelerated renal recovery from AKI upon lithium chloride injection. The lithium-promoted recovery in renal function was accompanied by improved histopathologic picture, as Demonstrated by pathology scores. Pathological pictures and scores demonstrated a significant improvement in lithium chloride (low dose:40mg/kg) treated rats than saline-treated. lithium chloride (high dose:80mg/kg) treated rats showed improvement in pathological picture but results were not significant.
Collectively, these data suggest that lithium chloride has an Obvious improving effect that promotes renal function recovery and kidney repair after AKI.