Propolis and its therapeutic effects on renal diseases: A review.

Propolis is produced by bees using a mixture of bees wax and saliva. It contains several bioactive compounds that mainly induce anti-oxidant and anti-inflammatory effects. In this review, we aimed to investigate the effects of propolis on kidney diseases. We used "Kidney", "Disease", "Propolis", "Renal", "Constituent", "Mechanism", "Infection", and other related keywords as the main keywords to search for works published before July 2023 in Google scholar, Scopus, and Pubmed databases. The search terms were selected according to Medical Subject Headings (MeSH). This review showed that propolis affects renal disorders with inflammatory and oxidative etiology due to its bioactive compounds, mainly flavonoids and polyphenols. There have been few studies on the effects of propolis on kidney diseases; nevertheless, the available studies are integrated in this review. Overall, propolis appears to be effective against several renal diseases through influencing mechanisms such as apoptosis, oxidative balance, and inflammation.

A standardized extract of Ziziphus jujuba Mill protects against adriamycin-induced liver, heart, and brain toxicity: An oxidative stress and biochemical approach.

Due to the antioxidant effects of the Ziziphus jujuba Mill (Z. jujuba), we investigated the liver, heart, and brain-protective effects of this herb against toxicity induced by adriamycin (ADR). In this study, Wistar rats were divided into 1) control, 2) ADR and 3, 4, and 5) treated groups orally administrated three doses of Z. jujuba hydroalcoholic extract for 1 month. The liver, heart, and brain were removed for evaluation of the oxidative markers. Blood samples were evaluated to determine the levels of Lactate dehydrogenase, total and direct bilirubin, alkaline phosphatase, Aspartate transaminase, and Alanine aminotransferase. Administration of Z. jujuba significantly decreased the biochemical enzymes compared to the ADR. Oxidative condition in treated rats with different doses of Z. jujuba was improved compared to the ADR group. Z. jujuba could decrease the oxidative injury through invigoration of the tissues antioxidant system. The mentioned hepatic and cardiac parameters levels improved during extract administration. PRACTICAL APPLICATIONS: In the first stage, our findings and other supplementary works have shown that administration of jujube extract has prevented the effects of histotoxicity caused by adriamycin, so it seems that in the next stage, the effects of this herbal plant on patients with tissue toxicity caused by adriamycin should be evaluated and if the results are positive in pharmacological studies, it should be used as a complementary drug in the treatment of these patients.

The testicular protective effects of standardised hydroalcoholic extract of Ziziphus jujuba Mill against adriamycin-induced toxicity.

In this study, because of the anti-inflammatory and antioxidant effect of the Ziziphus jujuba (ZJ), we assessed the protective properties of the ZJ extract against testis toxicity caused by Adriamycin in the rat. Twenty rats were grouped into (a) control, (b) Adriamycin, (c) ZJ group and (d) treatment group in which Adriamycin was administrated and the ZJ hydroalcoholic extract was used for three weeks. On the 21st day, two testes were removed to determine the oxidation markers and pathological evaluation. The levels of sex hormones were determined. Epididymis also was crushed, and its spermatozoa were evaluated as concentration, motility and normality. Adriamycin increased oxidative stress markers as well as Luteinising hormone, and follicle-stimulating hormone and decreased testosterone levels compared to control. In the treated group, the levels of the above markers improved. The decreased number and motility of spermatozoa in treatment group increased, and the increased rate of abnormal spermatozoa in this group decreased. Pathological evaluations also show the healing process of damaged testicular tissue in the group receiving the ZJ extract. The ZJ extract relatively improves oxidative stress, sperm characteristics, hormonal alternation and pathological changes. These findings reveal the probable role of ZJ effective compounds in repairing tissue damage.

Thymoquinone alleviates renal interstitial fibrosis and kidney dysfunction in rats with unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)-ß1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF-ß1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01-p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001-p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO-induced kidney fibrosis and dysfunction.

Nigella sativa extract is a potent therapeutic agent for renal inflammation, apoptosis, and oxidative stress in a rat model of unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) is a well-established experimental model to evaluate renal interstitial fibrosis. Current study is aimed to investigate the effects of Nigella sativa (NS) extract and renin-angiotensin system (RAS) blockade against kidney damage following UUO in rats. In this study, the rats received intraperitoneal injection of losartan (15 mg/kg), captopril (30 mg/kg), and two doses of NS extract (200 and 400 mg/kg) for 18 consecutive days. At the fourth day of the experiment, laparotomy was performed, and the left ureter was ligated. Sham-operated animals received saline as vehicle, and laparotomy without ureteral ligation was done. UUO was associated with significant increase in the expression of renal angiotensin II and monocyte chemoattractant protein-1, concentration of malondialdehyde and tumor necrosis factor-α, and the number of apoptotic cells when compared with sham group. Renal total thiol content and the activity of antioxidant enzymes were significantly reduced as compared with the sham group. However, treatment of obstructed rats with losartan, captopril, and NS extract significantly improved these renal impairments when compared with UUO group. Thus, NS extract, a potent antioxidant and anti-inflammatory herb, is a therapeutic agent to treat the UUO-induced kidney damage comparable with the well-known RAS inhibitors captopril and losartan.

Zataria multiflora extract and carvacrol affect cardiotoxicity induced by Adriamycin in rat.

Background Because of the antioxidant effects of Zataria multiflora (ZM) and carvacrol (CAR) and also the role of oxidative stress in the induction of cardiotoxicity induced by Adriamycin (ADR), the aim of this study was to investigate the improvement effects of ZM extract and CAR on cardiotoxicity induced by ADR in rats. Methods Twenty-eight male rats were randomly assigned to four groups including (1) the control group; (2) the ADR group, which received ADR intravenously at the beginning of the study and the (3) ZM+ADR and (4) CAR+ADR groups, which received ZM and CAR by gavage for 28 consecutive days and ADR as single dose. Blood samples were collected on days 0 and 28 to determine serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH). Also, cardiac tissue was removed for redox marker evaluation. Results In the ADR group, malondialdehyde (MDA) significantly increased and superoxide dismutase (SOD) activity and total thiol contents significantly reduced, as compared with the control group, while CAR administration significantly improved this condition. Treatment with ZM significantly increased the SOD activity and total thiol content, as compared with the ADR group. The level of LDH significantly increased on day 28 in the ADR group compared to the control group, and administration of ZM and CAR significantly decreased it. The SGPT and SGOT levels in the ADR group significantly increased, and CAR administration significantly reduced them. Conclusion The results indicate that the administration of ZM hydroalcoholic extracts and its active ingredient, CAR, could reduce the oxidative stress damage through promotion of the cardiac and systemic antioxidant system. Also, CAR administration demonstrated better improvement in cardiotoxicity with ADR in rats.

Protection Against Doxorubicin-induced Nephropathy by Plantago major in Rat.

INTRODUCTION: Nephropathy is an important side effect of doxorubicin. The aim of the current study was to investigate the protective effect of Plantago major extract against doxorubicin-induced functional and histological damage in rat's kidney. MATERIALS AND METHODS: Sixty Albino rats were randomly divided into 6 groups. Doxorubicin, 5 mg/kg, was injected intravenously on the 7th day of the study. Animals were treated with dexamethasone, 0.9 mg/kg, vitamin E, 100 mg/kg, and P major extract, 600 mg/kg and 1200 mg/kg, for 7 days before and 4 weeks after doxorubicin administration. Glomerular filtration rate, urea clearance, and urine glucose concentration were determined on the 1st day and 1, 2, 3 and 4 weeks after doxorubicin injection. Histological changes were also examined and the end of the study. RESULTS: Doxorubicin caused significant decreases in glomerular filtration rate and urea clearance and significant glycosuria and kidney damage. Urea clearance in the rats treated with P major showed no significant change between different days of the experiment. Administration of dexamethasone, vitamin E, and low- and high-dose P major significantly improved the glycosuria and kidney tissue damage. CONCLUSIONS: These findings suggested that hydroalcoholic extract of P major protected renal tissue against doxorubicin-induced nephropathy. The protective effects of P major on renal lesions associated with doxorubicin may be due to its antioxidant and anti-inflammatory actions.

Drug-induced Nephrotoxicity and Medicinal Plants.

Drug-induced nephrotoxicity is one of the most common causes of acute kidney injury. There are various agents that exert nephrotoxic effects through different pathogenic mechanisms. Aminoglycoside antibiotics, chemotherapeutic agents, radiocontrast media, and nonsteroidal anti-inflammatory drugs are among common nephrotoxic agents. In recent years, natural compounds are being increasingly used in the treatment of kidney diseases. Given many reports available on the curative effects of a variety of medicinal plants against drug-associated nephrotoxicity, we aimed to review the protective effects of medicinal plants on certain nephrotoxic drugs.

Kidney stone formation and antioxidant effects of Cynodon dactylon decoction in male Wistar rats.

OBJECTIVES: The antioxidant capacity impairs in kidney and urinary bladder of animals with stone disease. Herbal medicine can improve the antioxidant condition of renal tissue. Cynodon dactylon (C. dactylon) is a medicinal plant with antioxidative and diuretic properties and different preparations of this plant have shown promising effects in stone disease. Assessment of the whole plant decoction to prevent kidney stone disease as well as its antioxidant effects was the aim of this paper. MATERIALS AND METHODS: Fifty male Wistar rats were randomly divided into 5 experimental groups (n=10). One group was left without treatment and four groups received ethylene glycol (1% v/v) in drinking water for 6 weeks. Three doses of Cynodon dactylon aqueous decoction (12.5, 50 and 200 mg/kg BW) were added to the drinking water of groups 3-5. Finally, water intake, 24-hour urine volume, MDA, total thiol concentration and FRAP value were measured in the serum and kidney tissues. The CaOx depositions were evaluated by hematoxylin and eosin staining. RESULTS: Compared to the ethylene glycol-treated group, 200 mg/kg C. dactylon, lowered stone incidents, decreased urine volume, increased FRAP/g Cr (43%) and thiol content (p<0.05) with no significant alteration of water intake, MDA decreased significantly compared to C. dactylon 12.5 (p<0.01). Kidney weight increased and body weight decreased in ethylene glycol-treated group compared to the control group (p<0.05). CONCLUSION: A minimum dose of 200 mg/kg C. dactylon reduced stone formation and simultaneously increased total antioxidant power of serum and preserved MDA content and water.

Renoprotective Effect of Plantago Major Against Nephrotoxicity and Oxidative Stress Induced by Cisplatin.

INTRODUCTION: The aim of this study was to investigate the possible renoprotective effect of Plantago major extract against cisplatin-induced nephrotoxicity in rats. MATERIALS AND METHODS: Rats were divided into 6 groups. The first group was the control, group 2 was treated with cisplatin (7 mg/kg, single dose), and groups 3 to 6 received cisplatin with vitamin E (100 mg/kg) and Plantago major  extract at doses of 300 mg/kg, 600 mg/kg, and 1200 mg/kg, for 20 days. RESULTS: On day12, serum concentration of urea, creatinine, and potassium significantly increased and sodium concentration significantly decreased in the cisplatin group compared with the control rats. However, serum creatinine, urea, and potassium concentrations were significantly lower in all of the Plantago major groups compared to the cisplatin group. Also, there was a significant elevation in serum sodium concentration in the Plantago major 600 mg/kg group compared to the cisplatin group on day12. Injection of cisplatin caused a significant elevation in malondialdehyde concentration but a significant decrease in catalase activity and total thiol content compared to the control group. Plantago major extract at 1200 mg/kg significantly improved malondialdehyde concentration and total thiol content compared to the cisplatin group. Catalase activity with Plantago major significantly increased at all doses compared to the cisplatin group. CONCLUSIONS: The current study suggests that Plantago major extract and vitamin E are able to improve kidney function as well as oxidative stress in cisplatin-induced renal toxicity in the rat.

Renal injury, nephrolithiasis and Nigella sativa: A mini review.

OBJECTIVE: The incidence and prevalence of kidney stone is increasing worldwide. After the first recurrence the risk of subsequent relapses is higher and the time period between relapses is shortened. Urinary stones can be severely painful and make a huge economic burden. The stone disease may increase the vulnerability of patients to other diseases such as renal failure. Medicinal herbs are rich sources of antioxidants which are increasingly consumed globally for their safety, efficacy and low price. Nigella sativa is a spice plant that is widely used for prevention and treatment of many ailments in Muslim countries and worldwide. This review aims at investigation of the effects of Nigella sativa on renal injury and stone formation. MATERIALS AND METHODS: The scientific resources including PubMed, Scopus, and Google scholar were searched using key words such as: nephrolithiasis, urolithiasis, kidney/renal stone, renal injury, renal failure, urinary retention and black seed, black cumin, Nigella sativa and thymoquinone. RESULTS: N. sativa and its main component, thymoquinone showed positive effects in prevention or curing kidney stones and renal failure through various mechanism such as antioxidative, anti-inflammatory, anti-eicosanoid and immunomodulatory effects. The putative candidate in many cases has been claimed to be thymoquinone but it seems that at least in part, particularly in kidney stones, the herbal melanin plays a role which requires further investigation to prove. CONCLUSION: N. sativa and its components are beneficial in prevention and curing of renal diseases including nephrolithiasis and renal damages.

Topical effectiveness of kiwifruit versus fibrinolysin ointment on removal of necrotic tissue of full-thickness burns in male rats.

Formation of necrotic tissues is a major issue affecting treatment of full-thickness burns. This study was designed to compare topical effectiveness of applying kiwifruit versus fibrinolysin on removal of necrotic tissue of burns. Ten adult male Wistar rats were randomly assigned to three groups. For group 1, the right-side wounds were treated with kiwifruit and the other side with fibrinolysin. For group 2, the wounds on the right side were treated with kiwifruit or fibrinolysin, and the left sides were kept as control group 2. All wounds in group 3 were considered as control group 1. The control wounds were left to heal naturally. In each group and for each wound, the time of debridement were noted. The results indicated that for the wounds where kiwifruit was applied, the average time for removal of dead tissue was 5.7 days, which is significantly shorter than the average 18.5 days it took for treatment with fibrinolysin (p = 0.02). However, there were no significant differences between control wounds 1 and 2. Findings of the present study can open new horizons and provide a new treatment modality for patients with deep burns.

Effect of alcoholic extract of Nigella sativa on cisplatin-induced toxicity in rat.

INTRODUCTION: The aim of this study was to test whether Nigella sativa (NS) seeds can reduce cisplatin-induced toxicity. MATERIALS AND METHODS: Thirty rats were divided into 3 groups to receive distilled water (control group), cisplatin (3 mg/kg per body weight for 3 days), and cisplatin and alcoholic extract of NS (100 mg/kg per body weight). Biochemical and histopathologic parameters were compared between the three groups on days 14 and 42 of the study. RESULTS: Blood urea nitrogen increased in the cisplatin and NS groups on days 14 and 42 compared to day 0 (P < .001). It was significantly in the cisplatin than in the control group on day 14 (P < .001). Serum creatinine had a similar profile in the cisplatin and NS groups as blood urea nitrogen. Serum triglyceride increased in the cisplatin and NS groups on day 14, but it decreased on day 42 (P < .05). Urine glucose concentration decreased in the cisplatin group on days 14 and 42 compared to day 0 (P < .001), and the same trend was seen in the NS group (P < .001). Histology of the kidneys exposed to cisplatin showed significant kidney injury, but the rats treated with NS showed a relatively well-preserved architecture. CONCLUSIONS: Cisplatin-induced nephrotoxicity was confirmed in our study. Nigella sativa seeds had nonsignificant effects on biochemical parameters, although the histopathologic properties of the kidneys relatively recovered after NS use.

The beneficial effect of cynodon dactylon fractions on ethylene glycol-induced kidney calculi in rats.

PURPOSE: To assess the beneficial effect of different fractions of Cynodon dactylon (C. dactylon) on ethylene glycol-induced kidney calculi in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into control, ethylene glycol, curative, and preventive groups. The control group received tap drinking water for 35 days. Ethylene glycol, curative, and preventive groups received 1% ethylene glycol for induction of calcium oxalate (CaOx) calculus formation. Preventive and curative subjects also received different fractions of C. dactylon extract in drinking water at 12.8 mg/kg, since day 0 and day 14, respectively. After 35 days, the kidneys were removed and examined for histopathological findings and counting the CaOx deposits in 50 microscopic fields. RESULTS: In curative protocol, treatment of rats with C. dactylon N-butanol fraction and N-butanol phase remnant significantly reduced the number of the kidney CaOx deposits compared to ethylene glycol group. In preventive protocol, treatment of rats with C. dactylon ethyl acetate fraction significantly decreased the number of CaOx deposits compared to ethylene glycol group. CONCLUSION: Fractions of C. dactylon showed a beneficial effect on preventing and eliminating CaOx deposition in the rat kidney. These results provide a scientific rational for preventive and treatment roles of C. dactylon in human kidney stone disease.