Chemical analysis and antioxidant study showed that it contains fat, protein, fiber, carbohydrate, phenol and flavonoids, and it exhibited antioxidant activity. Studies have shown that bee bread is composed of 18.0% water, 7.79 g/100g total lipid, and 93.96% carbohydrates and the main fatty acids in bee bread are arachidonic …show more content…
and oleic acids [56, 57]. However, the composition might alter according to the source of pollen collection and plant types. A study of nine bee bread samples showed that the radical scavenging activity ranged from 72.5± 4.4 to 94.0±0.3% in ABTS reaction system and from 71±3.7 to 92.2±3.0% in DPPH reaction system, while the screening of phenolic compounds revealed that bee breed contained a high amount of kaempferol and trace amount of chrysin and apigenin [30].
The results of hematological parameters showed that aluminum decreases significantly Ht, Hb, RBC, MCV, MCH, and MCHC. Other studies showed similar results [8, 15, 58-61]. Aluminum chloride administration for 60 days significantly decreased total RBC, Hb concentration, PCV%, MCV, MCH, MCHC, RBCs osmotic fragility, serum catalase (CTA) activity, serum iron, TIBc, and serum ferrritin, and increased reticulocytes count. The use of propolis or malic acid normalized these parameters when were used with aluminum chloride [15]. Periodical injections of aluminum to rats over a period of three months caused significant decreases in Ht and Hb concentration, erythrocyte aggregate size and aggregation rate, and it disorganized erythrocyte membrane by altering its mechanical properties [60]. Furthermore, intraperitoneal aluminum injections significantly decreased Hb concentration, Ht and serum iron in rats [8]. Another study showed that aluminum increases leukocytes counts, erythrocyte osmotic fragility and decreases RBC, Hb and Ht, while there was no change in MCV, MCH, or MCHC [61].
It has been proposed that the mechanism of aluminum’s toxicity is a hemolysis caused by the generation of free radicals leading to the degradation of the cell membrane or due to alternation in iron level caused by aluminum [8,58] . Aluminum enhances heme oxygenase -1 expression through the ROS - mediated activation of c-Jun N-terminal kinase pathway, which may activate heme oxygenase and accelerate degradation of heme that causes hypochromic anemia [59]. Furthermore, aluminum decreases cytosolic ATP leading to activation of calcium- channels, and stimulation of cell membrane scrambling and cell shrinkage, a feature of hemolysis [62]. Aluminum causes increase in reticulocytes which is another feature of hemolysis [15].
Studies showed that aluminum decreased iron level and can interfere with iron in the erythrocytes because it shares several characteristics such as trivalency and it can share the same mechanism of absorption, distribution and metabolism [7,8]. Our previous study showed that honey, part of bee bread, caused significant elevation of iron level, Hb, and PCV [63]. Honey increased serum iron by 20% and decreased plasma ferritin by 11% in normal individuals. It also increased antioxidants. It has been found that bee pollen increased Hb, and serum iron in rats [64]. Therefore, honey and bee pollen increased Hb and PCV, partly, due to an increase iron in aluminum exposure. Further studies are needed. Also both they have an antioxidant activity which helps restoring hematological parameters changed induced by aluminum.
The elevation of liver enzymes might be a result of hepatic cellular injury. Similar aluminum toxicity has been reported by many studies [21, 22, 39, 40]. Aluminum chloride caused a significant increase in GGT, ALT, AST, ALP, and lipid peroxidation and these changes were alleviated by saffron, a spice derived from the flower of Crocus sativus, and honey [22]. Another study revealed that aluminum chloride causes a significant increase in alkaline phosphatase, AST, ALT and lactate dehydrogenase, and causes sinusoidal dilatation, congestion of central vein, lipid accumulation and lymphocyte infiltration in liver [21]. Our previous studies showed that honey, part of bee bread, caused amelioration of elevated liver enzymes during acute blood loss and food restriction [42]. Furthermore, we have found that honey feeding ameliorates the elevation in AST and ALT obtained following CCl4 administration in rats [43]. Another study showed that that chestnut bee pollen protects the hepatocytes from the OS and promotes the healing of the liver damage induced by CCI4 toxicity (65).
Regarding kidney parameters, aluminum causes a significant increase in BUN and a significant decrease in creatinine clearance.
It has no effect on SCr. The elevation of BUN might be due to renal injury or other mechanisms. Liver synthesizes urea and during liver injury low BUN is encountered. Therefore, the real mechanism of increasing BUN in setting of liver injury is not clearly identified. However, other studies showed that aluminum chloride increases both BUN and SCr [11,13, 18, 20]. In present study aluminum chloride was used for 28 days while the other studies use aluminum for longer period of time. This might explain why there was no change in serum creatinine in the present study. Recently, it was found that aluminum chloride administered for 40 days increases BUN and SCr and decreases urine volume and creatinine clearance [20]. This was accompanied by increased renal OS and inflammation. This is in agreement with our findings that aluminum decreases creatinine clearance. Another study showed that aluminum chloride used for eight weeks in rats causes elevation of BUN and SCr [11]. We have found that honey has reno-protective effect in acute blood loss, CCI4 toxicity and lead toxicity [42,43,47]. It also improved renal function in normal individuals which has been suggested due to increase nitric oxide and decreasing prostaglandins
[66].
Interestingly, the present data showed that aluminum increases leukocytes, monocytes and lymphocytes counts and CRP level. These are markers of inflammation [67]. Epidemiological data demonstrated that aluminum exposure can result in excess inflammatory activity within the brain (9). Furthermore, aluminum increases hepatic pro-inflammatory cytokines expression including interleukin-1β, tumor necrosis factor-α, and interleukin-6 [61]. CRP is a highly sensitive biomarker for systemic inflammation. High CRP level indicates an increased risk for cardiovascular disease, cancer, diabetes, and Alzheimer's disease. It is mainly synthesized in liver and in endothelial cells. It was shown that nanomolar aluminum up-regulates CRP expression in human brain microvessel endothelial cells. The results suggested that aluminum-induced CRP may in part contribute to a pathophysiological state associated with a chronic systemic inflammation of the human vasculature [68].
Albumin exposure caused OS and inflammation, and decreased activity of the antioxidant enzymes such as superoxide dismutase (SOD), CAT, and glutathione peroxidase (GPx) [23, 25, 27, 28,39,61] . Aluminum causes significant increase in the malondialdehyde (MDA) level and decrease in the activities of antioxidant enzymes in the brain cortex and blood [28]. Furthermore, it causes a significant increase in MDA, CTA, GPx, as well as a significant reduction in serum reduced GTS and MDA levels in rats and mice [18,23,25]. It was found that aluminum chloride exposure induces OS and suppresses kidney function [25].
The use of antioxidants such as taurine, omega3 fatty acid, resveratrol, gingerol, nigella sativa oil, honey, propolis and saffron ameliorate aluminum induced heap-renal toxicity and restore antioxidant system [16, 18, 23-25, 27, 28]. Therefore, bee bread constituents, honey and bee pollen, might encounter or ameliorate albumin toxicity by their antioxidants activity. More studies are needed. Furthermore, honey and bee pollen might have a synergistic effects. This needs to evaluate the effect of each and in combination in aluminum toxicity.
The use of Lactobacillus plantarum CCFM639 caused a significant reduction in the mortality in rats, a decrease in intestinal aluminum absorption and in accumulation of aluminum in the tissues, and an alleviation of hepatic, renal, and cerebral OS [17]. It has been reported that Lactobacillus plantarum is of the dominant lactobacilli in the honey stomach of honeybee [69]. Therefore, these bacteria may be present in the honey part of the bee bread and helping to protect in aluminum toxicity.
Conclusion
Bee bread, a composition of pollen, honey and bees` enzymes, exhibited antioxidant activity and has a considerable protective effect in aluminum induced toxicity in rats. It prevented anemia, and ameliorated the elevation of CRP, monocytes and leukocytes counts, and reverse elevation of liver enzymes and BUN toward normal level. The mechanism of action might be related to antioxidant and anti-inflammatory activity of bee bread. More studies are needed to verify this possibility.