Testosterone restores TM3 and TM4 cell viability, reduces reactive oxygen species generation, and protects against atrazine-induced stereological changes in rat testes.

In this study, we performed the stereological examination of rat testes and evaluated the protective effect of testosterone against atrazine (ATZ) toxicity in TM3 Leydig and TM4 Sertoli cells. Testosterone intake in rats increased the volumetric density of the seminiferous tubules; tubular diameter; germinal epithelial height; number of spermatogonia, primary and secondary spermatocytes, round spermatids, Sertoli cells, and Leydig cells; and Johnsen scores compared with the values after ATZ treatment (p < 0.05). Furthermore, testosterone increased the viability of TM3 cells and reduced reactive oxygen species (ROS) generation in TM4 cells compared to the ATZ-treated group. In conclusion, exogenous testosterone intake maintains testicular morphometry and spermatogenesis in rats, and minimizes cell death and ROS generation in testicular cell lines exposed to ATZ. However, TM4 cells are more responsive to testosterone-mediated regulation of ROS generation induced by ATZ than TM3 cells.

Effect of co-administration of gallic acid and quercetin or gallic acid and rutin on impaired spermatogenesis and oxidative damage in a busulfan-treated rat model.

Gallic acid (GAL), rutin (RUT), and quercetin (QUE) are common antioxidant agents in fruits and vegetables with intriguing pharmacological effects. In the present study, we compared the therapeutic outcomes of GAL + QUE in comparison with GAL + RUT co-treatment in a busulfan (BUS) model of testicular injury in Wistar rats. BUS (4 mg kg-1 body weight (b.w) was injected intraperitoneally daily for 4 days. GAL + RUT or GAL + QUE (20 mg kg-1 b. w) was delivered by oral gavage for 52 days. Examination of the testes of BUS-treated rats both biochemically and under light microscopy revealed an increased level of lipid peroxidation, DNA fragmentation, glutathione-S-transferase, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase and acid phosphatase with a concomitant decrease in the level of antioxidants: glutathione, ascorbic acid, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, suggesting testicular injury. Tissue sections confirmed the testicular injury-induced by BUS, including diminished spermatogenesis score index, tubular diameter, gonado-somatic index, testis weight, epithelia thickness and higher percentage of aberrant tubules. GAL + QUE co-administration had better recovery effects than GAL + RUT on the biochemical markers and protected against BUS-induced testicular damage. GAL + QUE treatment regimen has better capacity to maintain the antioxidant capacity of the testes and is more potent at reducing BUS-induced oxidative damage compared to GAL + RUT.

Ascorbic acid attenuates gasoline-induced testicular toxicity, sperm quality deterioration, and testosterone imbalance in rats.

The present study evaluated the protective effect of ascorbic acid (ASCB) against gasoline fumes (PET) induced testicular oxidative stress, sperm toxicity, and testosterone imbalance in Wistar rats. Twenty-four (24) male albino rats (75 ± 16 g) were randomized into three experimental groups (N = 8). The control group: received normal saline, PET group: exposed to PET 6 h daily by inhalation in an exposure chamber and PET + 200 mg ASCB/kg body weight group: exposed to PET 6 h daily by inhalation and administered ASCB per os. Treatment of ASCB and PET exposure was done thrice and five times weekly for a period of 10 weeks respectively. ASCB co-treatment prevented PET-induced increases in the oxidative stress markers (glutathione, glutathione S-transferase, superoxide dismutase, catalase, hydrogen peroxide generation, nitric oxide, and lipid peroxidation) and serum testosterone concentration (p < .05). Sperm quality was low and those with damaged heads and tails increased alongside histological injuries in the PET-exposed rats, which were also minimized with ASCB administration. ASCB protected against PET-induced oxidative stress, sperm, and testis damage in rats.

COVID-19 vaccinations: The unknowns, challenges, and hopes.

The entire world has been suffering from the coronavirus disease 2019 (COVID-19) pandemic since March 11, 2020. More than a year later, the COVID-19 vaccination brought hope to control this viral pandemic. Here, we review the unknowns of the COVID-19 vaccination, such as its longevity, asymptomatic spread, long-term side effects, and its efficacy on immunocompromised patients. In addition, we discuss challenges associated with the COVID-19 vaccination, such as the global access and distribution of vaccine doses, adherence to hygiene guidelines after vaccination, the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, and vaccine resistance. Despite all these challenges and the fact that the end of the COVID-19 pandemic is still unclear, vaccines have brought great hope for the world, with several reports indicating a significant decline in the risk of COVID19-related infection and hospitalizations.

Fluted pumpkin seeds protect the spermatogenesis score index and testicular histology of caffeine treated rats.

The present study was designed to evaluate the protective effect of fluted pumpkin seeds (FPS) against caffeine (CAFF) induced testicular toxicity in rats. Thirty young healthy male Wistar rats (196 ± 12 g) were randomly organized into five sets of six animals per each group: control, caffeine (CAFF; 50 mg kg-1 bw) and FPS co-treatment groups (CAFF + 50 mg FPS, CAFF + 100 mg FPS and CAFF + 200 mg FPS kg-1  bw). CAFF and FPS were administered daily and twice per week respectively by oral gavage for 40 days. CAFF treatment decreased testicular lactate dehydrogenase enzyme activity level, which was attenuated on co-administration with FPS at 50 and 100 mg kg-1  bw. Furthermore, CAFF decreased seminiferous epithelia thickness and spermatogenesis score index and increased the number of tubules with abnormal histological features, which were attenuated on co-administration with FPS at 50 mg kg-1  bw much more than at the higher doses (p < 0.05). CAFF did not affect malondialdehyde and glutathione concentrations and glutathione peroxidase (GSH-Px) activity in the testes whereas FPS co-treatment at the higher doses elevated glutathione level and GSH-Px activity and did not affect spermatogenesis score index at the highest dose (200 mg kg-1  bw). Testicular malondialdehyde concentrations remained unaffected in all FPS co-treatment groups. Overall, FPS is able to minimize the CAFF-induced testicular injury at lower than at the higher tested doses.

Curcumin improves the protective effects of quercetin against atrazine-induced testicular injury in adult Wistar rats.

This study evaluated the beneficial protective effect of cotreatment of curcumin (CUR) and quercetin (QUE) on atrazine (ATZ)-induced testicular toxicity in rats. ATZ challenge diminished luteinizing hormone, follicular stimulating hormone, testosterone and myeloperoxidase enzyme activity, but these effects were attenuated on co-treatment with CUR and QUE. Also, co-treatment of CUR + QUE was better than separate administration of QUE at diminishing malondialdehyde and glutathione and improving tumour necrosis factor-α concentration, germ cell numbers (spermatogonia, spermatocytes and round spermatids) and epididymal sperm quality. Histologically, smaller sized tubules with degenerated epithelia and few germ cells were seen in the seminiferous tubules of the ATZ group whereas CUR + QUE pretreatment improved the histo-morphologic features of the tubules compared to the ATZ group and was also better than separate administration of QUE. We conclude that CUR can improve the protective effects of QUE against ATZ-induced testicular injury by enhancing the levels of reproductive hormones, recovering testicular biochemical parameters and improving the histological features of the testes.

The protective effect of rutin against busulfan-induced testicular damage in adult rats.

Here, we studied the protective effect of rutin (RUT) against testicular damage caused by busulfan (BUS) in rats. Adult male Wistar rats were intraperitoneally injected with BUS (4 mg/kg body weight at day 7 and 14), and then treated with RUT (30 mg/kg body weight) by gavage thrice weekly for 60 days. The results showed that BUS-induced increase in 3ß-hydroxysteroid dehydrogenase (3ß-HSD) was significantly decreased by RUT, whereas 17ß-HSD activity and plasma testosterone concentration remained unaffected (p > 0.05). It was also observed that RUT inhibited BUS-induced increase in nitrite concentrations and myeloperoxidase enzyme activities in the plasma and testes (p < 0.05). Similarly, BUS-induced decrease in glutathione and increase in malondialdehyde concentrations in the testes were significantly normalized to control values by RUT. Finally, RUT administration showed some tendency to improve the architecture of the seminiferous epithelium of the rat's testes after BUS treatment. Overall, RUT inhibited BUS-induced oxidative damage and inflammation in the testis of an experimental rat model.

The protective effect of fluted pumpkin seeds against atrazine-induced testicular injury.

The present study evaluated the protective effect of fluted pumpkin seeds (FPS) on atrazine (ATZ)-induced testicular damage. Twenty adult male Wistar rats were divided into four groups of five animals each. The control animals (Group A) received corn oil (2 mL/kg body weight), Group B animals received 50 mg ATZ/kg body weight by gavage, while Groups C and D received 50 mg ATZ/kg body weight once a week in addition to the gavage of 25 mg FPS/kg body weight and 50 mg FPS/kg body weight respectively for 60 days. The results showed that testicular myeloperoxidase activity and nitrite concentration were decreased in all groups compared to the control value. The increase in malondialdehyde and decrease in glutathione concentrations in group B were abrogated in group C (p < 0.05) but not in group D animals. The increase in γ-glutamyl transpeptidase and decrease in lactate dehydrogenase enzyme activities in the group B animals were also normalized to control values in group C but not in group D animals. Interestingly, the testis of the group D animals showed massive depletion of germ cells and the diameter of the seminiferous tubules of these animals were decreased compared to all other groups. However, the number of motile sperms, abnormal sperms and sperm count in Group D animals were similar to the ATZ-treated animals and lower than control values. In conclusion, FPS protected against ATZ-induced testicular damage but can also harm the testis at a higher dose.

Gallic acid ameliorates busulfan-induced testicular toxicity and damage in mature rats.

Here, we studied the protective effect of gallic acid (GAL) as a potent anti-oxidant and anti-inflammatory agent against damage caused by busulfan (BUS) in the testes of adult rats. The adult Wistar rats were assigned as control, BUS: was intraperitoneally (i.p.) treated with busulfan (15 mg/kg, day 7 and 14), GAL + BUS: was co-treated with busulfan (i.p., 15 mg/kg, day 7 and 14) and orally treated (per os) with gallic acid (60 days, 20 mg/kg) and GAL: was treated with gallic acid (per os, 60 days, 20 mg/kg). The results showed that GAL co-treatment increased the numbers of spermatogonia (Type A and B), spermatocytes (primary and secondary) and round spermatids, along with the tubular diameter, epithelial height and gonado-somatic index. In addition, BUS-induced increase in 3ß-hydroxysteroid dehydrogenase and γ-glutamyl transpeptidase activities were inhibited on GAL co-treatment. Similarly, BUS-induced decrease in gluthathione concentration, catalase and superoxide dismutase activities along with increase in myeloperoxidase activity and malondialdehyde concentration were significantly normalized to control values on GAL co-treatment. Busulfan-induced elimination of tubular germ cells was completely prevented by GAL. Overall, GAL may inhibit BUS-mediated spermatogenesis arrest via decreasing inflammatory-mediated oxidative stress in a rat experimental model.

Plants in the management of male infertility.

This review attempts to collate existing data and provide the perspectives for future studies on the effects of plants on the male gonads. For many of these medicinal plants such as Lepidium meyenii, Rupus coreanus, Tribulus terrestres, Panax ginseng, Petasites japonicas, Apium graveolens, Eurycoma longifólia, Pedalium murex, Corchorus depressus, Mucuna pruriens, Astragalus membranaceus, Nigella sativa, Crataegus monogyna, Fagara tessmannii, Phaleria macrocarpa, Anacyclus pyrethrum, Cynomorium songaricum and Morinda officinalis, the mechanism of actions of their active principles and crude extracts has been shown in both laboratory animals, in vitro, and human studies, and includes their antioxidant, anti-inflammatory, spermatogenesis-inducing, aphrodisiac, smooth muscle relaxing and androgenic properties. Several active chemical leads including glucosinolates, anthocyanins, protodioscin, ginsenosides, sesquiterpenes, phyto-oestrogens, quassinoids, diosgenin, thymoquinone, proanthocyanidins and bajijiasu isolated from these plants are known to have target effects on the testis, but efforts have been limited in their application at the clinical level. There still appear to be many more extracts of medicinal plants that have not been characterised to determine the phytochemicals unique to them that have target effects on the gonads. Further, collaborative efforts at isolating pro-drug candidates from medicinal plants for studies at the molecular, cellular and clinical level towards elucidating their mechanisms of action on the testes are therefore warranted in the light of the current male fertility crisis.

Morphometric Evaluation of the Seminiferous Tubules and the Antioxidant Protective Effects of Gallic Acid and Quercetin in the Testis and Liver of Butyl Phthalate Treated Rats.

The antioxidant protective effects of gallic acid (GAL) and quercetin (QUE) against oxidative stress induced by di-butyl phthalate (DnBP) in the liver and testis of rats were evaluated in this study. Adult albino Wistar rats (180-225 g) were treated with QUE or GAL (50 mg/kg) alone or in combination with DnBP (1 mL/kg) for 15 days. After treatment, tissue samples were taken for determination of glutathione and malondialdehyde levels, and superoxide dismutase and catalase activities. Serial sections of the testis and liver were stained with haematoxylin and eosin for microscopy and seminiferous tubular morphometry. As expected, DnBP induced oxidative stress was evident by increased malondialdehyde level in both organs. Co-treatment with GAL or QUE reversed the malondialdehyde by 45.42, 37.44 and 37.57%, 23.32% and catalase by 52.21, 70.15 and 85%, 38.14% in the testis and liver respectively whereas superoxide dismutase activity and glutathione level were differently modulated parallel to histopathological improvement in both tissues. The seminiferous tubular diameter, epithelial height, epithelial germ cell count and tubular length were significantly decreased by 11.09, 51.91, 40.65 and 11.10% respectively versus control values after DnBP treatments and were attenuated on co-treatment with GAL or QUE. Co-treatment with GAL afforded better protective effects in both tissues but QUE treatment alone appeared more effective than GAL on the investigated morphometric data. It seems likely that GAL or QUE prevented the tissue damage but the antioxidant profiles of the liver and testis are different in response to the oxidative stress.

Protective effects of Anthocleista djalonensis A. Chev root extracts against induced testicular inflammation and impaired spermatogenesis in adult rats.

This study was designed to explore the protective effects of methanol (Meth, 200 mg kg-1 body wt) and aqueous ethanol (Eth-OH, 200 mg kg-1 body wt) extracts of Anthocleista djalonensis roots on testicular inflammation induced by lipopolysaccharide (LPS, 5 mg/kg body wt) and depletion of tubular germ cells induced by busulfan (15 mg/kg body wt) in rats after 60 days of oral administration. As expected, LPS stimulation of the animals significantly increased serum and intra-testicular interleukin-6 and serum nitrite levels which were significantly inhibited in the Eth-OH + LPS and Meth + LPS animals. The increase in testicular and not serum myeloperoxidase activity that was induced by LPS treatment was synergistically increased in the Eth-OH + LPS animals, whereas it was inhibited in the Meth + LPS animals compared to LPS-treated animals. Furthermore, the administration of the Eth-OH or Meth extracts protected against busulfan-induced depletion of tubular germ cells and promotes the re-population of the seminiferous tubules with germ cells (spermatogonia, spermatocytes and round spermatids) at different stages of development. The extracts were found to contain 7'-oxaspiro [cyclopropane-1,4'-tricyclo [3.3.1.0 (6,8)] nonan-2'-one], cis,cis-7,10-hexadecadienal, hexadecanoic acid, methyl ester, hexadecanoic acid, ethyl ester, 9,12-octadecadienoic acid, methyl ester, and 9,12-octadecadienoic acid (Z,Z)-) which may partly explain the observed anti-inflammatory effects. In conclusion, Meth extracts of A. djanonesis have better anti-inflammatory effects than the Eth-OH extract for the management of impaired testicular function due to inflammation. However both extracts exhibited protective effect on the histology of the testis allowing for the recovery of spermatogenesis.

Effects of Anthocleista djalonensis root extracts on reproductive hormones and testicular marker enzymes in adult male Wistar rats.

This study evaluated the effect of methanol and aqueous ethanol root extracts (200 mg/kg body weight) of Anthocleista djalonensis on sex hormone concentrations and testicular marker enzymes of adult rats after 60 days of administration followed by 60 days of treatment withdrawal. The results showed no significant changes in testosterone and follicle-stimulating hormone (FSH) levels during the 60 days of extract treatment. Interestingly, 60 days after treatment withdrawal, there was an increase in intratesticular and serum testosterone and serum FSH in the methanol but not aqueous ethanol extract post-treatment groups. Intratesticular 3ß-hydroxysteroid dehydrogenase (3ß-HSD) activity remained unaffected while that of 17ß-HSD increased slightly during treatment of both extracts and the increase reached a statistical significance level (p < .05) during post-treatment. Gamma-glutamyltranspeptidase activity in the testis of the methanol but not aqueous ethanol extract-treated animals remained high during post-treatment compared to initial treatment values. Phytochemical analysis of the plant extracts showed that phenol and flavonoid constituents were higher in the methanol than the aqueous ethanol extract and has higher antioxidant activity. Altogether, post-treatment effect of the extract on the testis was more effective than treatment-related effect and the methanol extract appears to have better and consistent effects on the investigated parameters probably due to higher antioxidant activity conferred to it by its phenolic and flavonoid contents.

Effects of co-exposure to atrazine and ethanol on the oxidative damage of kidney and liver in Wistar rats.

Both ethanol (EtoH) and atrazine (ATZ) have hepatic and nephro-toxic effects in rats. In the present study, the toxicity of EtoH (5 g kg-1) on the kidney and liver in the absence or in the presence of different doses of ATZ (50, 100, 300 mg kg-1) was evaluated after 21 days in rats. Results showed that the mixture effects on catalase and superoxide dismutase activities were more severe in both tissues compared to EtoH alone, especially as the dose of ATZ was increased. Hepatic malondialdehyde level (an index of lipid peroxidation) was increased from 20.32% in the EtoH +50 mg kg-1 ATZ-treated rats to 34% in the EtoH +300 mg kg-1 ATZ-treated rats compared to the EtoH values. Renal malondialdehyde values remain as high as 81% in the EtoH-treated rats and the different combine exposure groups. Furthermore, as the dose of ATZ in the mixture was increased, serum uric acid level increased compared to the EtoH values. When the EtoH +300 mg kg-1 ATZ-animals were pretreated with curcumin (an antioxidant), the histopathological changes and peroxidative damages in both tissues were blocked. The exposure of EtoH-treated rats to ATZ enhanced renal and hepatic peroxidative damages in rats.

Rutin ameliorates oxidative stress and preserves hepatic and renal functions following exposure to cadmium and ethanol.

CONTEXT: Rutin (RUT) is an antioxidant flavonoid with well-known metal chelating potentials. OBJECTIVE: This study was designed to evaluate the protective effects of RUT against cadmium (Cd) + ethanol (EtOH)-induced hepatic and renal toxicity in rats. MATERIALS AND METHODS: Wistar rats were treated with Cd (50 mg/kg) alone or in combination with EtOH (5 mg/kg) and RUT (25, 50 and 100 mg/kg) for 15 days. After treatment, the liver, kidney and serum were removed for biochemical assays by spectrophotometric methods. RESULTS: Serum, hepatic and renal malondialdehyde (MDA) levels were highest in the Cd + EtOH group and lowest in Cd + EtOH animals co-treated with the highest dose of RUT (2.98 ± 0.34, 10.08 ± 2.32, 4.99 ± 1.21 vs. 1.69 ± 0.33, 6.13 ± 0.28, 3.66 ± 1.12 µmol MDA/mg protein, respectively). The serum level of Cd was increased in the Cd + EtOH treated animals compared to Cd + EtOH animals co-treated with 100 mg/kg RUT (2.54 ± 0.08 vs. 1.28 ± 0.04 ppm). Furthermore, RUT at the highest dose protected against Cd + EtOH-induced elevation of bilirubin and uric acid levels as well as activities of lactate dehydrogenase and γ-glutamyl transferase (62.86 ± 2.74 vs. 122.52 ± 6.35 µmol/L; 1.77 ± 0.35 vs. 3.23 ± 0.55 mmol/L; 9.56 ± 1.22 vs. 16.21 ± 1.64 U/L; 288.92 ± 40.12 vs. 159.8 ± 18.01 U/L). The histo-pathological changes in the liver and kidney were also reduced in the Cd + EtOH animals co-treated with RUT in a dose-dependent manner. DISCUSSION AND CONCLUSION: RUT protected against the combined effects of Cd + EtOH on hepatic and renal functions and improved the antioxidant defence system in the blood.

Effect of Ethanolic Extract from Seeds or Pods of Xylopia Aethiopica (Dunal) A. Rich (Annonaceae) on the Testicular Function of Adult Male Rats.

Xylopia aethiopica (Annonaceae) is used in some folk medicines and widely consumed as a spice in some parts of Nigeria. Its efficacy as an anti-androgenic substance has warranted the attention of African scholars. This study evaluated the enzymatic activity of lactate dehydrogenase (LDH), γ-glutamyl transferase (γ-GT), sperm quality (motility, count, morphology), testosterone level and histo-pathological changes of the testis of rats chronically treated with ethanolic extract of the pods (without seeds), seeds, and fruits (pods + seeds) of Xylopia aethiopica. Male Wistar (224-246 g) rats were treated with the extract of the pods, seeds, and fruits of Xylopia aethiopica at the dose of 0, 50, 100, and 200 mg/kg body wt. for 60 days. Serum biochemistry, sperm quality and histo-pathological examination of the testis were assessed for any treatment-related adverse effects. After treatment with Xylopia aethiopica, testosterone level was decreased dose-dependently in the animals treated with the seed extract compared to all other groups. The enzymatic activities of LDH and γ-GT were higher in rats treated with the seed and fruit extracts compared with those treated with the pods. The numbers of motile sperm, and counts were decreased while the numbers of sperm with morphological defects were higher in rats treated with the seed and fruit extracts compared to the control. Histopathological changes of the testis were also more severe in rats treated with the highest dose of the seed extract. We conclude that the compounds related to the anti-infertility effects of Xylopia aethiopica are present in the seeds.

Curcumin protects against gallic acid-induced oxidative stress, suppression of glutathione antioxidant defenses, hepatic and renal damage in rats.

Curcumin (Cur) and gallic acid (Gal) are major food additives. Cur has well-known antioxidant properties, whereas Gal has both antioxidant and pro-oxidant effects. The present study investigated the effects of oral administration of Gal with or without Cur on antioxidant enzymes activities, glutathione (GSH) and the enzymes in its metabolism in rat liver in vivo and markers of tissue damage in the serum. Results showed that the increase in serum creatinine level, alkaline phosphatase and lactate dehydrogenase activities by Gal treatment were inhibited by combined administration of Gal and Cur. The decrease in GSH-peroxidase, GSH-S-transferase, superoxide dismutase and GSH-reductase activities by Gal treatment were inhibited when both Gal and Cur were administered together. The malondialdehyde concentration and catalase activity were significantly increased following administration of Gal but not when the administration of Gal was combined with Cur. Finally, the increase in GSH level was seen following administration of Cur alone or in combination with Gal but not with Gal alone. These results suggest that Gal might induce oxidative stress in the rat liver and affect renal function that can be inhibited by the combined administration of Gal and Cur.

Quercetin ameliorates atrazine-induced changes in the testicular function of rats.

The protective effect of quercetin (QT) on atrazine (ATZ)-induced testicular damage in rats was investigated. Sexually mature male Wistar rats (weighing 220-250 g) divided into four groups with six animals in each group were given ATZ (120 mg kg(-1); 1/16 of the median lethal dose for an oral dose) and/or QT (10 mg kg(-1)) daily via gavage for 16 days. By the end of day 16, rats given ATZ alone had significantly lower sperm counts, daily spermatozoa production, and sperm motility and significantly higher abnormal sperm numbers than the untreated control rats. The rats given ATZ alone also had significantly decreased 3ß-hydroxtsteroid dehydrogenase (HSD) and 17ß-HSD activities than the control rats. Lactate dehydrogenase activity and malondialdehyde levels were significantly increased, whereas superoxide dismutase activity decreased but glutathione levels remain unaffected after ATZ exposure. These changes were reversed toward control values in the QT + ATZ-treated animals, though the sperm motility was 28% below the control levels but was still higher than in the ATZ-treated rats. The results indicate that QT might improve testicular function of rats exposed to ATZ, but its protective effect on sperm motility might be partial.

Selenium and rutin alone or in combination do not have stronger protective effects than their separate effects against cadmium-induced renal damage.

CONTEXT: Selenium (Se) and rutin (RUT) are antioxidants that protect against tissue damage. OBJECTIVE: In this study, the separate and combine protective effects of RUT and Se against cadmium (Cd)-induced renal damage were evaluated in rats. MATERIALS AND METHODS: Wistar rats were treated by gavage to RUT (30 mg/kg) or Se (0.15 ppm) or Cd (200 ppm) in drinking water alone or in combination (30 mg/kg RUT +0.15 ppm Se + 200 ppm Cd). Corn oil was used as vehicle (2 mL/kg). After a 5-week treatment period, rat kidneys were removed for biochemical assays and histopathological examination. Se and Cd levels were evaluated by flame atomic absorption spectrophotometry. RESULTS: The malondialdehyde and glutathione levels as well as superoxide dismutase and catalase activities in the Cd-treated animals were increased compared with control values (0.056 ± 0.0003 versus 0.011 ± 0.0005 µmol/mg; 0.005 ± 0.0006 versus 0.00085 ± 0.0002 µg/mg; 1.62 ± 0.09 versus 0.48 ± 0.12 units/mg; 650 ± 25 versus 361.89 ± 31 µmol H2O2/mg, respectively). Cd treatment was also associated with decreased renal Se concentration (4.19 ± 0.92 versus 7.73 ± 0.7 µg/g dry weight), increased alkaline phosphatase (0.07 ± 0.0015 versus 0.033 ± 0.0019 unit/mg), acid phosphatase (0.029 ± 0.0021 versus 0.015 ± 0.0016 unit/mg), and lactate dehydrogenase (0.032 ± 0.004 versus 0.014 ± 0.0027 unit/mg) activities, respectively, and with evidence of severe renal damage. The combination of RUT and Se or their separate effects prevented the Cd-induced oxidative renal damage. However, their combine effects do not have stronger effects than their separate effect against Cd-induced renal damage. DISCUSSION AND CONCLUSION: RUT and Se function as potent antioxidant in the protection of renal damage induced by Cd.

Kolaviron, a natural flavonoid from the seeds of Garcinia kola, reduces LPS-induced inflammation in macrophages by combined inhibition of IL-6 secretion, and inflammatory transcription factors, ERK1/2, NF-κB, p38, Akt, p-c-JUN and JNK.

BACKGROUND: Kolaviron (Kol-v), an important component of Garcinia kola seed has a variety of biologic activities, including anti-inflammatory properties. METHODS: We tested the ability of Kol-v to block signalling pathways implicated in lipopolysaccharide (LPS)-induced inflammatory gene expression in RAW 264.7 macrophage cell line. RESULTS: When macrophages pre-treated with Kol-v (15 and 25µM) were activated with LPS, phosphorylation of p38 and p-c-JUN but not IκBα degradation and phosphorylation of NF-κB (p65), ERK1/2, and IκBα were blocked. Furthermore, Kol-v suppressed LPS-induced increase in the expression of IL-18 gene and LPS-induced decrease in the mRNA expression of IP-10 but it had no effect on the LPS-induced decrease in the gene expression levels of IL-1α, IL-33, IL-1ß, and IFNß1-1. When macrophages pre-treated with Kol-v (50 and 100µM) were activated with LPS, phosphorylation of Akt, ERK1/2, IκBα, and NFκB (p65) but not that of CREB was blocked by Kol-v. The protective effect of Kol-v on the LPS-induced phosphorylation of the mitogen activated protein kinase (MAPK) family member JNK was only observed at 100µM. At all concentrations of Kol-v (0-100µM) tested in this study, there was no effect of Kol-v on LPS-induced secretion of the pro-inflammatory cytokine TNF-α but a concentration dependent inhibition of Kol-v on IL-6 secretion was observed. CONCLUSION: Kol-v interferes with LPS signalling by reducing the activation of several inflammatory transcription factors and that its inhibitory action on IL-6 secretion correlates with inhibition of ERK1/2, p38, Akt, p-c-JUN and JNK signalling pathways. GENERAL SIGNIFICANCE: The anti-inflammatory potential of Kol-v via inhibition of IL-6 secretion in RAW macrophage was established in this study.