Leading to 27.1% of death on earth, cardiovascular disease remains the leading cause of death on the globe for more than a decade [1]. Control of cardiovascular risk factors is thus imperative for reducing the morbidity and mortality of the global population [2]. The primary cause of these vascular diseases is atherosclerosis and subsequent formation of lesions inside the coronary and cerebral arteries [3]. Pathogenesis of atherosclerosis is multifactorial and many modifiable and non-modifiable risk factors have been identified [4]. These risk factors collectively contribute to the development, progression and rupture of atherosclerotic plaques [5]. Of the modifiable risk factors, hypercholesterolemia which is estimated to cause 4.5% of global death and 2.0% of global disability adjusted life years [6] is the most important [7]. Extreme levels of blood cholesterol accelerate atherogenesis and lowering high blood cholesterol reduces the incident of Coronary heart disease [8].

Botanical dietary supplements can improve cardiovascular health and prevent atherosclerosis at several steps [9]. Dietary recommendations for reducing cardiovascular diseases have been focused on the change or reduction in fat or cholesterol intake [10]. One of the strategies for obtaining a tailor-made diet for this disease is the use of foods that contain nutrients which reduce intestinal cholesterol absorption [11]. Sesamum indicum Linn belongs to the family Pedaliaceae and several lines of evidence from traditional to modern medicine have confirmed its various medicinal properties [12-14]. This plant contains significant amount of diverse phytochemicals [15] which have been shown to serve as promising natural antioxidants for both food preservation and medicinal applications [13] (Table 1).

Table 1: Diet Compositions after the Establishment Hypercholesterolemia. (g kg^-1).

Sesamum indicum L. Seed Oil, which constitutes about 55% of the seed [16], has 80% of its fatty acid content composed of oleic and linolenic acids and 16% saturated fatty acid [17-19]. It has been appreciated for its antihypercholesterolemic ability [18,20]. However, no study has been conducted to relate Sesamum indicum oil’s antihypercholesterolemic ability to the reversal of kidney dysfunction characteristic of severe hypercholesterolemia [21]. This study thus evaluates the effect of Sesamum indicum (benniseed) oil on kidney functions of albino rats induced with hypercholesterolemia.

Collection of sample

Sesame seeds were purchased from Oja-Oba market in Ado-Ekiti. It was identified and authenticated at the Herbarium Section of Plant Science Department, Ekiti State University, Ado-Ekiti, Nigeria. It was cleaned, washed and sundried.

Extraction of oil

Oil was extracted using Soxhlet extractor and n-hexane as the solvent (bpt 40-60°C).

Experimental procedure

Twenty four male albino rats were randomly assigned into four groups (A, B, C and D) comprising of six rats each. Group A served as the normal control while group B, C and D served as the test group. Initially, animals in groups (B, C and D) were fed with 20% fat + 1% cholesterol for two weeks to establish hypercholesterolemia. Thereafter, rats in groups C and D were treated with feed supplemented with 5% and 10% Sesamum indicum seed oil respectively. They were maintained on this dietary regimen for four weeks and their weights monitored.

Preparation of serum and kidney homogenate: At the end of the experiment, rats were fasted overnight, anaesthesized and blood samples were collected by cardiac puncture into lithium-heparin bottles. It was centrifuged at 3,000 rpm for 10 min and the plasma was separated and kept until required for analysis. The kidneys were removed, de-capsulated, homogenized and centrifuged at 3,000 rpm for 20 mins. The supernatant was collected for further analysis.

Biochemical analysis: From the serum, the concentrations of urea, creatinine, sodium, potassium and alkaline phosphatase were measured and from the kidney homogenate, concentration of alkaline phosphatase were measured.

Statistical analysis: The results are expressed as Median ± Interquartile ranges. Kruskal-Wallis Test [22] was used to test for differences in the groups. Differences were considered to be statistically significant at P<0.05.

Sesamum indicum Linn Oil has been demonstrated to reduce hypercholesterolemia by significantly decreasing TC, TG, LDL and LDL/HDL ratio, and significantly increasing the HDL-C [18] and by maintaining normal circulatory levels of apoA and apoB, SGOT, SGPT, glucose and insulin [20] in animals induced with hypercholesterolemia. This study tests the ability of Sesamum indicum oil in preventing the impairment of kidney functions caused by hypercholesterolemia and presents a pliable means by which Sesamum indicum oil reduces blood cholesterol levels in cases of hypercholesterolemia. Hypercholesterolemia has been implicated in the impairment of kidney functions [21]. This is evident in Table 2 as hypercholesterolemia induced by 1% cholesterol in the diet of male albino rats led to kidney dysfunction measured by the increase in the concentrations of urea, creatinine, sodium and potassium in the blood.

Table 2: Effect of Sesamum indicum L. Seed Oil Supplementation on the Kidney Function Parameters of Hypercholesterolemic Rats.

Urea is a byproduct from protein breakdown. About 90% of urea produced is excreted via the kidney [23]. In kidneys, urea is filtered out of blood by glomeruli and is partially reabsorbed with water [24]. Meanwhile, Creatinine which is commonly measured as an index of glomerular function [25] is a waste product from muscle creatine that is used as energy source during muscle contraction. The normal range of serum creatinine is 0.2-0.8 mg/dl for rats [26] and like urea, it is excreted exclusively through the kidney. Damage to the kidney will thus render the kidney inefficient to excrete both urea and creatinine, therefore causes their accumulation in the blood [27]. Hence, a higher than normal level of blood urea and creatinine will indicate kidney damage. The most frequently used clinical indices for estimating renal function depends upon concentration of urea in the serum. It is useful in differential diagnosis of acute renal failure and renal conditions where blood urea nitrogen is increased [28]. As indicated in Table 2, feeding hypercholesterolemic rats with 5% and 10% Benniseed (Sesamum indicum) oil significantly reduced the rising serum urea but not creatinine levels. The inability to reduce creatinine level may be in part because creatinine levels in the blood will not be raised above the normal range until 60% of total kidney function is lost [27]. Urea and creatinine have been reported to be less reliable markers for kidney function [29].

Another tool for accessing damage to kidney is serum electrolytes The test for electrolytes includes the measurement of sodium, potassium, chloride and bicarbonate levels [30]. Although sodium is the most concentrated electrolyte in the extracellular fluid [31], Potassium is the most convincing electrolyte marker of renal failure [32,33]. The combination of decreased filtration and decreased secretion of potassium in distal tubules during renal failure cause increase plasma potassium [32]. As indicated in Table 2, feeding hypercholesterolemic rats with 5% Benniseed (Sesamum indicum) oil significantly reduced the rising serum sodium and potassium concentrations of the rats. Thus implying that supplementation with 5% beniseed oil helps to ameliorate the injury imposed on the kidney by the hypercholesterolemic diet.

Yet another tool for diagnosing damage to the kidney like other internal organs is marker enzymes [33-35]. Alkaline phosphatase is a marker enzyme for the plasma membrane and endoplasmic reticulum [36] of the tissue studied. It is often employed to assess the integrity of plasma membrane [33] since it is localized predominantly in the microvilli of the bile canaliculi, located in the plasma membrane. The significant increase in the Serum ALP activity of the hyper-diet group B in Table 3 following the administration of hypercholesterolemic diet may be due to de novo synthesis of the enzyme molecules. Since alkaline phosphatase hydrolyses phosphate monoesters, the enzyme’s hyperproduction could constitute a threat to the life of the cells that are dependent on a variety of phosphate esters for their vital process, as it may lead to indiscriminate hydrolysis of phosphate ester metabolite of the liver, an important biochemical symptom of cytolysis. Consequently, this may adversely affect the facilitation of the transfer of metabolites across the cell membrane [37].

Table 3: Effect of Sesamum indicum L. Seed Oil Supplementation on Kidney and Serum Alkaline Phosphatase Concentrations of Hypercholesterolemic Rats.

However the significant decrease (P<0.05) in the Serum ALP activities of the treated groups C (5% benniseed oil) and D (10% benniseed oil) shows a distinct correction of the assault caused by hypercholesterolemic diet in group B leading to a lower activity than even the Control (group A). Increase in serum ALP and a corresponding decrease in kidney alkaline phosphatase activities of the hypercholesterolemic rats can be suggestive of damage to the kidney leading to leakage to extracellular fluids [37]. However, on supplementing with Sesamum indicum oil, significant reduction in ALP activities was observed in the kidney with no corresponding increase in the serum thus suggesting that the benniseed oil appears to alleviate the assault inflicted on the kidney by the hypercholesterolemic diet.

In summary, findings arising from the present study suggest that Sesamum indicum oil can reverse kidney damage caused by hypercholesterolemia. This positive effect of Sesamum indicum oil further substantiates previous studies and jointly postulate therapeutic value of Sesamum indicum oil in clinical conditions associated with hyperlipidemia and hypercholesterolemia.