The connection between DM and bone damage associated with mineral metabolism dysfunction is a common phenomenon found in both humans and rats. Insulin is a potential bone growth regulator, since osteoblasts have insulin receptors [9
] as well as IGF1 receptors, which can also mediate the effects of insulin. In vitro
insulin directly stimulates osteoblast proliferation [10
] and when administered locally, over the calvariae of adult male mice, it produces two- to three-fold increases in the histomorphometric indices of bone formation [11
]. It is also known that insulin promotes amino acid cell intake in cultured bone. Collagen synthesis is increased too, due to a possible direct effect of insulin on the osteoblasts. Insulin also regulates the activity of glycogen synthase in cultured osteoblast-like cells [12
Some researchers have reported that a longer history of type 1 diabetes is correlated with decreasing bone mass [13
]. The mechanisms that lead to a decreased bone biomechanical competence, besides the decreases in BMD, are collagen glycosylation alterations generated by hyperglycaemia, in the same way as increased haemoglobin glycosylation, which is expressed as HbA1C. These advanced glycation end products (AGE) and their receptors (RAGE) play an important role in bone metabolism and bone strength [2
Our study results are in agreement with the results of other experimental in vivo
studies conducted on diabetic rats that were treated with vegetal polyphenols found in red wine or green tea [15
]. The increased levels of reactive oxygen species (ROS) and decreased antioxidant defense can cause DNA damage and direct protein inhibition. The main substrates targeted by free oxygen radical activity are polyunsaturated fatty acids in membrane phospholipids, the modification of which results in cell framework and function disorganization. The end product of these reactions is MDA. SOD is the first line of defense against ROS and is active in catalyzing superoxide radical detoxification [17
]. SOD is the most abundant antioxidant enzyme in animals. A study assessing the systemic oxidant-antioxidant status throughout the evolution of the disease was carried out. SOD decomposes superoxide anion into hydrogen peroxide and oxygen at almost the highest possible reaction rate. The superoxide radical is involved in various physiological and pathophysiological processes. It is produced in respiratory and cytochome P450 electron transport chain reactions as a by-product. A high amount of this product is also generated by activated neutrophils and macrophages during oxidative burst.
Numerous experimental studies have proven the ability of vegetal polyphenols to diminish lipid peroxidation and to reduce LDL oxidation, probably through the uptake of lipid-peroxil radicals and through lipooxygenases activity reduction, thus delaying atheroma plate formation [18
]. Polyphenols are able to penetrate tissues, particularly those in which they are metabolized, but their ability to accumulate in specific target tissues needs to be further investigated. Despite the increasing amount of available data, final conclusions on the bioavailability of most polyphenols are difficult to draw and further studies are necessary [20
In drug-induced diabetes mellitus with polyphenol protection, the antioxidant quality of the serum increases, the lipid profile is improved and hyperglycemia is significantly ameliorated [22
]. Two mechanisms were suggested by means of which vegetal polyphenols act as antioxidants within a biological system under oxidative stress conditions [25
]: a mechanism according to which polyphenols act as reducing agents or electron donors, converting lipid peroxides in lipid hydroxides or phospholipid peroxides in phospholipid hydroxides, inhibiting lipid peroxidation; another mechanism through which vegetal polyphenols may chelatise transitional metallic ions.
The polyphenolic extract obtained from the Sambucus nigra
fruit improves the lipid profile significantly (P
< 0.001) and reduces the atherogenic risk significantly (P
< 0.001). Hyperglycemia is significantly improved (P
< 0.01). Aqueous elder (Sambucus nigra
) extracts have been shown to have an insulin-like effect on in vitro
glucose uptake [27
]. Whereas hyperglycemia can result in the generation of free radicals through several biochemical pathways (nonenzymatic glycation, the polyol pathway, and glucose autoxidation), the mechanisms underlying oxidative damage in diabetes are still unclear. Free radicals can result in antioxidant defense consumption and enhanced susceptibility to lipid peroxidation. The study showed reduced TAS in type 1 diabetic against nondiabetic control subjects. These results indicate that the alterations in the glucose utilizing system and oxidation status in rats increased by streptozotocin were partially reversed by polyphenolic extract delivery.
The TAS reduction in type 1 diabetic rats was associated with increasing HbA1c and diabetes duration. Thus, increased serum levels of the total antioxidant status and HbA1c were associated with osteoporotic risk reduction in diabetic rats.
In diabetic males, the evolution of bone mineral density compared with the area, measured throughout the experiment, suffered a significant decrease, especially in the femur. In diabetic male rats that were given polyphenolic extract, these differences were statistically minimum.
The highest BMD difference compared with the area was recorded in the spine, followed by the cervical spine. As for the comparison between the BMD of the two groups of males, the most statistically significant difference compared with the area was noticed in diabetic males undergoing polyphenol treatment.
The BMC in the groups of males had the most statistically significant difference compared with the area in the femur of diabetic males, followed by the cervical spine of males undergoing polyphenol treatment. As for the spine, the highest BMC difference compared with the area was found in diabetic males with polyphenol intake, whereas the highest overall significant difference was noticed in diabetic males.
Except for the overall comparison, comparisons between the BMC and BMD of diabetic males revealed significant statistical differences in the spine, lumbar, and femur areas. In diabetic males that were given polyphenol treatment, a 4–7% decrease of their body fat was noticed in all analyzed sampled, at the end of the experiment.
The study revealed reduced TAS in type 1 diabetic against nondiabetic control subjects. The understanding of bone biology may open the way for new osteoporosis treatments. The positive skeletal effects of polyphenols at dietary achievable levels are interleukin-6 mediated [28
The experiment shows the benefits of natural polyphenols extracted from the Elder (Sambucus nigra) fruit on osteoporosis regression in diabetic male rats. Extremely low bone mineral density in diabetic rats is improved by polyphenol delivery. Significantly low body fat percentages in diabetic rats are also improved by polyphenol intake. By carefully extending these results to humans, one may conclude that a dietary intake rich in natural polyphenols would lead to the regression of diabetes complications in general and osteoporosis in particular, in diabetic human patients. Osteoporosis regression due to the Sambucus nigra extract proves the benefits of polyphenols used to treat chronic diabetes mellitus complications.