1. Introduction

Today, obesity is a health threat in developed and developing countries. The most important disorders caused by weight gain and obesity are fatty liver disease, type 2 diabetes, and kidney failure [1]. In obese people, blood pressure rises to meet the needs of higher metabolism. Increased pressure inside the glomerulus can cause serious damage to the kidneys and increase the risk of chronic kidney disease in a long period. It can also be a risk factor for nephrolithiasis and several kidney malignancies, including kidney cancer [2]. The kidneys are involved in regulating the body’s osmolarity, stabilizing the internal environment (i.e. fluids and electrolytes) of the body, stabilizing the pH of body fluids, and also synthesizing and releasing substances, such as prostaglandins and erythropoietin [3]. 

The kidneys are the main route for the excretion of metabolic wastes, such as creatinine, urea, and uric acid. Increased serum levels of these three indicators imply a decrease in clearance and inability of the kidneys to excrete them from the blood; therefore, they can be used as an indicator to measure renal function and efficiency [4]. Estrogen can inhibit collagen synthesis in glomerular mesangial cells by modulating the activity of mitogen-activated protein kinase, angiotensin II, and transforming growth factor beta. It also limits glomerulosclerosis and prevents renal cell apoptosis by suppressing AP-1 expression. Therefore, estrogen can have a protective effect on the kidneys, and postmenopausal women are at risk for kidney disease, including kidney stones [5].

Glomerular Filtration Rate (GFR) is usually the most desirable indicator of renal function; however, due to the risks and side effects, difficulty in measurement, and its high cost, it is less used in clinical measurements. Therefore, other methods, such as measuring creatinine concentration and blood urea are used to measure GFR [6]. Increased urea and creatinine levels in the blood are caused due to kidney failure because of injury and destruction of the pseudopodia of glomerular podocytes, resulting in reduced contact with the glomerular base membrane and reduced glomerular filtration [7]. 

Exercise influences renal hemodynamics and electrolytes and changes the volume of body fluids and temperature, which can increase the body’s demand for food and excretion. It also is effective for various body systems, including the urinary system, and adapts it to physical activity. Kayakan et al. (2017) showed that the below maximum aerobic exercise increased blood creatinine and uric acid levels in the subjects, but this increase was not significant compared with the control group [8]. Novak et al. (2016) also reported a decrease in uric acid, an increase in urea, and no significant change in creatinine [9]. Straznicky et al. (2011) observed that 12 weeks of aerobic exercise reduced creatinine and increased GFR [10]. Kayasan et al. (2017) also reported that serum creatinine levels increased significantly in young and healthy subjects after cycling activity below the maximum level [8].

In recent years, much attention has been paid to the importance of medicinal plants. Medicinal plants have several advantages, including degradability, lower toxicity, and fewer side effects than chemical synthetic drugs. Bunium persicum (Boiss.), with the Persian name of Zire kuhi (wild mountain cumin), has medicinal properties, including anti-cancer, anti-microbial, and anti-flatulence effects and lowers blood sugar levels. The major constituents of wild mountain cumin are gamma-terpinene, vinyl aldehyde, caryophyllene, and flavonoids, and due to the high content of phenolic compounds, it has been considered as a strong antioxidant [11].

Kidney cells have the highest contact with free radicals, and wild mountain cumin seems to protect kidney health by its strong antioxidant properties. It is also a diuretic and helps to remove kidney and bladder stones and can reduce creatinine and Blood Urea Nitrogen (BUN) levels [12]. Zoe et al. showed that 8 weeks of cumin consumption significantly reduced creatinine, BUN, and urinary albumin levels [13]. Hosseinzadeh et al. reported that cumin consumption can prevent and even treat inflammation and kidney damage by reducing creatinine and glutathione (GSH) [14].

Minerals play an important role in kidney health. It has been observed that the amount of these micronutrients is lower in people with a history of kidney diseases than in healthy people. Regarding the improper functioning of the kidneys, the balance of electrolytes and minerals is lost leading to several complications [15]. Iron is an essential metal that with several important cellular processes plays a vital role in maintaining and sustaining life. Due to its ability to cause oxidative stress, its transport and metabolism are strongly controlled by the body, especially the small intestine, liver, and kidneys. It has been shown that in people with chronic and acute kidney damage, iron levels in the kidneys are increased associated with proteinuria, hemoglobinuria, and bleeding. Therefore, iron is an important therapeutic intervention for these patients [16]. 

After witnessing an insignificant reduction of iron and iron reserves after aerobic exercise, Dehghan et al. (2012) stated that this could be due to increased excretion through sweating, excretion of hemoglobin from the urine as well as mechanical damage and destruction of red blood cells [17]. Pompano et al. (2017) reported an increase in iron and ferritin after 8 weeks of aerobic exercise [18]. Skisi et al. (2017) reported increased serum levels of iron, calcium, and magnesium following 4 weeks of aerobic exercise [19].

Treatment of kidney diseases is mainly through medication and in more severe cases, dialysis and kidney transplantation, which are associated with high costs, pain, and side effects. Therefore, the benefits of exercise and cumin consumption can be used as a non-invasive, healthy, and hygienic method, which is also cost-and time-effective. Most studies in this field have been done on young people and athletes. Therefore, due to the effect of obesity on kidney disease, as well as the possible impact of exercise and cumin on improving kidney function, and because so far no research in Iran has examined the effects of exercise, cumin and kidney function simultaneously, this study aimed at determining the effect of 8 weeks of aerobic exercise in water with and without consuming wild mountain cumin on renal function factors and the level of minerals in blood samples of obese postmenopausal women.

2. Materials and Methods

The present experimental study with pretest and posttest design was performed. on 29 obese and inactive postmenopausal women with an average age of 57.75±9.71 years, the height of 156.38±4.74 cm, the weight of 73.91±9.23 kg, and a Body Mass Index (BMI) of 30.25±4.25 kg/m2. In the first step, to collect samples, information was announced through public announcements and calls in swimming pools in Mashhad city. The inclusion criteria were as follows: A. BMI above 25 kg/m2; B. Age range of 50-65 years, C) passing at least 2 years since the onset of menopause; D. Lack of specific and underlying diseases, and being under no compulsion to take medication; E. No participating in sports activities at least two months before the research; F. Physical health and no mobility or sports restrictions. 

After completing the preparation form for physical activity by the candidates, written consent was obtained from them. In this type of study, the sample size is usually calculated with a smaller number of subjects due to specific training conditions, the long training protocol, and high laboratory costs [20]. This clinical trial (IRCT20180124038494N1) was approved by the Ethics Committee of Mashhad University of Medical Sciences (Ethics Code: IR.MUMS.REC.1395.386).

In the next step, 30 qualified and volunteer postmenopausal women were randomly divided into 3 groups. One of the subjects was excluded from the statistical population due to non-compliance with the researchers’ recommendations and the lack of continuous attendance, and finally, the number was reduced to 29. The exercise group (first group) included 9 subjects, the supplement group (second group) included 10 subjects, and the exercise+supplement group (third group) included 10 subjects. The training protocol consisted of 8 weeks of aerobic exercise in water in three 45-60 min sessions per week at 65-75% of the maximum heart rate. 

All training sessions took place in the shallow part of the water pool. The exercise process included warming up, stretching, aerobic, flexibility, cooling down, and recovery. To consider the principle of overload during the training period, first, the number of movements was increased, then the rest time was reduced, and the speed of movements was increased. In the practice intervention, the principle of exercise diversity was also applied. Also, the subjects who needed supplements infused 3 g of cumin seeds daily in 200 ml of water at 80 degrees for 10-15 min and consumed them in 8 meals (at the same time and one hour before lunch or dinner) for 8 weeks [21]. 

The body composition of the subjects was measured using a BioSpace body measurement device (Inbody 720, South Korea). To measure height, the Seca measuring rod (220, Germany) with a sensitivity of 0.01 m was used. Subjects were asked to refer to a medical diagnostic laboratory at 8 am with a fasting period of 8-12 h to perform blood sampling in two stages (48 h before the first intervention and 48 h after the last research intervention). Each time, 10 cc of blood was taken from antecubital veins of the left arm of the subjects while they were sitting and resting. In this study, a syringe (G23-19) with a capacity of 10 cc was used and a 21-needle was used to prevent hemolysis. To prepare the serum, first, the blood in the test tube was clotted at room temperature for 20 min, then using a 24-tube Pars Azma brand centrifuge (made in Iran) for 15 min and at a rate of 2500 rpm, the serum was separated from the blood, and finally, it was stored in a freezer at -70°C. 

In order to measure the level of renal function, creatinine, urea, and uric acid indices, Pars Azmun kit (Iran) and BT-3000 Biotecnica autoanalyzer (Italy) were used. Pars Azmun kit was also used to measure minerals. The subjects were asked to write down their diet in the Dietary Recall (DR) questionnaire three days prior to the initial blood draw and to follow the same diet in the final blood draw. 

The collected data were analyzed using SPSS V. 20 software and the significance level was considered to be P≤0.05. Mean±SD of the data were calculated using descriptive statistics and to ensure that the data distribution was normal, the Kolmogorov–Smirnov (K-S) nonparametric test was used. To compare intra-group means before and after the intervention, a paired t-test was used, whereas a repeated measures ANOVA test was used to compare inter-group means.

3. Results

Table 1 shows the individual and anthropometric characteristics of the subjects in the three groups. The Kolmogorov–Smirnov test results showed that there were no significant differences between the age (P=0.531), weight (P=0.946), height (P=0.284), and BMI (P=0.621) variables; therefore, the data were normally distributed. The mean age of the participants in the study was 57.75±9.71 years.

Table 2 presents the intra-group, interactive, and inter-group changes of the creatinine, urea, and uric acid averages. The results showed that changes in creatinine, urea, and uric acid levels were not statistically significant among the group (P>0.05). In the exercise group, urea and uric acid levels increased slightly insignificantly (P>0.05) and creatinine was almost unchanged. In the supplement group, urea and uric acid levels decreased and creatinine increased slightly, but these changes were not statistically significant (P>0.05). In the exercise + supplement group, urea and creatinine levels increased slightly, but this increase was not significant (P>0.05) and the level of uric acid remained almost unchanged. Comparing the inter-group means of the three variables studied, it was found that the inter-group and interactive changes in none of the variables were statistically significant (P>0.05).

The intra-group, interactive, and inter-group mineral changes are also listed in Table 2. As can be seen, the intra-group changes in the exercise group significantly reduced for the iron level (P=0.001) and increased for the zinc level (P=0.041). Also, the intra-group changes in the supplement group significantly increased for the iron level (P=0.001), and the intra-group changes in the training + supplement group significantly increased for the zinc level (P=0.010). Interdisciplinary changes in the iron level were also significant (P=0.001).

4. Discussion

The results of the present study showed that none of the renal functional factors in the studied groups changed significantly. These results are consistent with the results of Sahin et al. (2017) and Zio et al. (2017), and inconsistent with the results of Hosseinian et al. (2016) who reported a decrease in serum levels of these indicators as well as of Kieh and Cheng results (2009) reporting an increase in their levels [7, 22, 23]. The reason for the discrepancy between the results of this study and other studies and the lack of significant changes in the three indicators may be due to differences in blood sampling time. In this study, blood sampling was performed 48 h after the last research intervention, while in other studies, blood sampling was performed immediately after the last research intervention. 

The study that examined the short-term effects of exercise on renal function, reported that rhabdomyolysis and hemodynamic changes in renal blood, changes in the permeability of the glomerular membrane, changes in the electrical charge of the membrane and blood acidity, as well as hormonal and enzymatic changes due to exercise, may increase glomerular permeability and impaired tubular reabsorption, and may cause low- and high-weight plasma protein excretion in the urine [24]. Therefore, it is necessary to observe a time interval of at least 48 h between the last training session and blood sampling so that the temporary and short-term effects of exercise on renal function are eliminated and only its long-term effects remain. On the other hand, the type of training program and the weather conditions are also very important. Physical activity on land and hot weather increases perspiration and intensifies the excretion of certain wastes, including urea and uric acid [25]. 

Our used intervention was water exercises. In this condition, the body’s heat excretion increases through conduction and convection, and the amount of perspiration decreases. This could be in the reason for the lack of reduction in the indicators examined [23]. Long-term effects of exercise in the aquatic environment on renal function include decreased systolic and diastolic blood pressure, increased oxygen uptake by the kidneys and decreased proteinuria and cystatin C. It can also cause significant changes in renal hemodynamics and protein excretion, which reduces the intense plasma flow activity of the kidneys and leads to a decrease in GFR. Among the short-term effects of exercise are changes in body fluid volume and excretions from nutritional needs. These changes also affect GFR and urea absorption after a long period of exercise and subsequently affect renal function indices [26]. However, in the present study, aerobic exercise in water did not significantly change the renal characteristics. Therefore, the reason for the lack of a significant change can be the difference in the intensity and duration of the training program, the length of the training period, the age and weight of the subjects, the type of statistical population, and their level of physical fitness.

Cumin has antioxidant compounds, including flavonoids, which have protective effects on kidney tissue and improve the condition of tubular cells and increase the efficiency of these tubules. These compounds also reduce the formation of free radicals and AGE. Oxygen oxidation properties play a vital role in various biological applications, such as food preparation and electron transfer to produce Adenosine Triphosphate (ATP). Oxygen is essential for living, but it can oxidize substances inside the cell and play a destructive role. It can also be converted to highly active forms, such as superoxide radicals, hydroxyl radicals, and hydrogen peroxide, which can damage the DNA of cells or destroy essential enzymes and structural proteins. It can also trigger uncontrolled chain reactions, such as autoxidation and peroxidation [27]. The use of substances containing polyphenolic antioxidants increases the activity of antioxidant enzymes, including catalase. Antioxidant enzymes responsible for destroying free radicals (hydroxide and superoxide) are harmful and reduce oxidative stress. 

One of the most important polyphenols is Epigallocatechin Gallate (EGCG), which in many cases, has stronger antioxidant properties than ascorbic acid and vitamin E. Polyphenols are strong adsorbents for free radicals due to the phenols. Polyphenols also can induce antioxidant enzymes, such as glutathione peroxidase, glutathione reductase, quinone reductase, and superoxide dismutase in various tissues [28]. In the present study, however, taking 8 weeks of cumin supplementation did not significantly change the functional characteristics of the kidney. It seems that the quantity and quality of supplementation were not adequate; therefore, the expected results were not achieved. Accordingly, it is suggested that cumin supplements of different quantities and qualities be applied in future similar studies.

The results of the present study showed that intra-group changes in zinc, in the exercise and exercise+supplement groups, significantly increased. Various studies have shown that exercise and physical activity can increase serum levels. A reason for the increase can be muscle damage and leakage of zinc into the extracellular fluid and blood flow. Exercise stress also increases the release of zinc from the liver. Serum zinc levels are associated with the severity and duration of the exercise. Medium- to high-intensity aerobic exercise leads to an increase, and the exercise below the maximum heart rate leads to a decrease in zinc levels [29]. Therefore, increased zinc level in the exercise and exercise+supplement groups was not unexpected. 

Another result of the present study was a significant decrease and increase in the iron index in the exercise and supplement groups, respectively. These changes were also significant in inter-group comparisons. Iron deficiency caused by aerobic exercise is generally due to decreased intestinal absorption [30]. Another possible justification for reducing iron intake through exercise is that athletes lose about 0.4 mg of iron with 1 L sweat [31]. It has been noted that substances with small molecular weight, such as sugars, ATP, and possibly amino acids act as iron repellents. During aerobic exercise, glycogenolysis is increased in the body that releases liver sugar into the blood vessels to produce more ATP in the carb cycling. Therefore, blood sugar levels increase due to increased growth hormone, glucagon, thyroxine, and epinephrine during exercise and it is possible to excrete more iron through special mechanisms [32]. On the other hand, cumin is a rich source of iron, zinc, and manganese that can be a source of these elements, especially iron in people with iron deficiency. In addition, cumin increases intestinal absorption and iron storage [33]. Therefore, a significant increase in the iron level in the supplement group can be justified.

5. Conclusion

The results of the present study showed that 8 weeks of aerobic exercise in water with and without taking wild mountain cumin could not significantly affect the functional factors of the kidneys. It is suggested that in the future, similar studies regarding the exercise and supplementation protocol be conducted because the interventions used in this study did not appear to have a significant effect on renal function. Meanwhile, aerobic exercise in water decreased, and consumption of cumin increased the iron level. Also, the exercise+supplement and exercise groups experienced a significant increase in the zinc level.

Ethical Considerations

Compliance with ethical guidelines

All ethical considerations were observed. This research is approved by the Ethics Committee of the Mashhad University of Medical Sciences (Ethics Code: IR.MUMS.REC.1395.386).

Funding

This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

Authors' contributions

Research design and idea, writing the original manuscript, review the final version of the manuscript: Nahid Beyjeh; Writing the article, review the final version of the manuscript: Fahimeh Sadat Jamali; Conducting the research protocol, writing the original manuscript, review of the final version of the manuscript: Razieh Rezaei, Mehri Ghalandarabadi.

Conflicts of interest

The authors declared no conflict of interest.

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